Author: "Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)" - Searchworks@Jio Institute Digital Library Search Results

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713 results on '"Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)"'

1. Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

Author: Marangon, Iris, Silva, Amanda, Guilbert, Thomas, Kolosnjaj-Tabi, Jelena, Marchiol, Carmen, Natkhunarajah, Sharuja, Chamming's, Foucault, Ménard-Moyon, Cécilia, Bianco, Alberto, Gennisson, Jean-Luc, Renault, Gilles, Gazeau, Florence, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Immunopathologie et chimie thérapeutique (ICT), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Langevin - Ondes et Images (UMR7587) (IL), Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), ANR-10-NANO-0008,NANOTHER,Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d'oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie(2010), ANR-10-LABX-0096,SEAM,Science and Engineering for Advanced Materials and devices(2010), Bos, Mireille, NANOTECHNOLOGIES ET NANOSYSTEMES - Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d'oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie - - NANOTHER2010 - ANR-10-NANO-0008 - P2N - VALID, Science and Engineering for Advanced Materials and devices - - SEAM2010 - ANR-10-LABX-0096 - LABX - VALID, Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Immunopathologie et chimie thérapeutique ( ICT ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Langevin ondes et images, Centre National de la Recherche Scientifique ( CNRS ) -ESPCI ParisTech-Université Paris Diderot - Paris 7 ( UPD7 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), ANR-10-NANO-0008,NANOTHER,Hybrides multifonctionnels à base de nanotubes de carbone et de nanoparticules d’oxyde de fer fonctionnalisés pour des applications en imagerie et en thérapie ( 2010 ), and ANR-11-LABX-086 - ANR-11-IDEX-05-02,LabEx SEAM,Science and Engineering for Advanced Materials and devices
Subjects: elastography, photothermal therapy, administration & dosage, Antineoplastic Agents, methods, Mice, pathology, therapy, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, cancer, tumor microenvironment, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, carbon nanotubes, Nanotubes, Carbon, Lasers, Hyperthermia, Induced, Nanostructures, Disease Models, Animal, Photochemotherapy, Carcinoma, Squamous Cell, Elasticity Imaging Techniques, Heterografts, Chimie/Chimie thérapeutique, Research Paper
Abstract: Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment. journal article research support, non-u.s. gov't 2017 2017 01 01 imported
Published: 2017

2. LARS2 variants can present as premature ovarian insufficiency in the absence of overt hearing loss

Author: Anne Sophie Neyroud, Joëlle Rudinger-Thirion, Magali Frugier, Lisa G. Riley, Maud Bidet, Linda Akloul, Andrea Simpson, David Gilot, John Christodoulou, Célia Ravel, Andrew H. Sinclair, Marc-Antoine Belaud-Rotureau, Elena J. Tucker, Sylvie Jaillard, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), The University of Sydney, Clinique mutualiste La Sagesse, La Trobe University [Melbourne], Charles Darwin University [Australia], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Melbourne, Murdoch Children's Research Institute (MCRI), and This work was supported by a CHU Rennes grant (Appel à Projets Innovations 2019 to SJ), an Australian NHMRC program grant (1074258 to AHS), NHMRC fellowships (1054432 to EJT, 1062854 to AHS) and an Australian Mito Foundation grant (EJT). Part of this work was performed under the Rare Diseases Functional Genomics program, supported by the Luminesce Alliance—Innovation for Children’s Health, a not for profit cooperative joint venture between the Sydney Children’s Hospitals Network, the Children’s Medical Research Institute, and the Children’s Cancer Institute. It has been established with the support of the NSW Government to coordinate and integrate pediatric research. Luminesce Alliance is also affiliated with the University of Sydney and the University of New South Wales Sydney (LGR). The research conducted at the Murdoch Children’s Research Institute was supported by the Victorian government’s operational infrastructure support program. The Chair in Genomic Medicine awarded to JC is generously supported by The Royal Children’s Hospital Foundation.
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetics, Genetics (clinical)
Abstract: International audience; Premature ovarian insufficiency (POI) affects 1 in 100 women and is a leading cause of female infertility. There are over 80 genes in which variants can cause POI, with these explaining only a minority of cases. Whole exome sequencing (WES) can be a useful tool for POI patient management, allowing clinical care to be personalized to underlying cause. We performed WES to investigate two French sisters, whose only clinical complaint was POI. Surprisingly, they shared one known and one novel likely pathogenic variant in the Perrault syndrome gene, LARS2. Using amino-acylation studies, we established that the novel missense variant significantly impairs LARS2 function. Perrault syndrome is characterized by sensorineural hearing loss in addition to POI. This molecular diagnosis alerted the sisters to the significance of their difficulty in following conversation. Subsequent audiology assessment revealed a mild bilateral hearing loss. We describe the first cases presenting with perceived isolated POI and causative variants in a Perrault syndrome gene. Our study expands the phenotypic spectrum associated with LARS2 variants and highlights the clinical benefit of having a genetic diagnosis, with prediction of potential co-morbidity and prompt and appropriate medical care, in this case by an audiologist for early detection of hearing loss.
Published: 2022

3. Remdesivir for the treatment of hospitalised patients with COVID-19: final results from the DisCoVeRy randomised, controlled, open-label trial

Author: Florence Ader, Maude Bouscambert-Duchamp, Maya Hites, Nathan Peiffer-Smadja, Julien Poissy, Drifa Belhadi, Alpha Diallo, Christelle Delmas, Juliette Saillard, Aline Dechanet, Claire Fougerou, Minh-Patrick Lê, Gilles Peytavin, Noémie Mercier, Priyanka Velou, Sarah Tubiana, Xavier Lescure, Emmanuel Faure, Saad Nseir, Jean-Christophe Richard, Florent Wallet, François Goehringer, Benjamin Lefèvre, Antoine Kimmoun, François Raffi, Benjamin Gaborit, Jean Reignier, Jean-Philippe Lanoix, Claire Andrejak, Yoann Zerbib, Firouzé Bani-Sadr, Bruno Mourvilliers, François Danion, Yvon Ruch, Raphaël Clere-Jehl, Vincent Le Moing, Kada Klouche, Karine Lacombe, Guillaume Martin-Blondel, Fanny Vardon-Bounes, André Cabié, Jean-Marie Turmel, Lionel Piroth, Mathieu Blot, Élisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Guillaume Thiery, François Bénézit, Rostane Gaci, Joy Mootien, Sébastien Gallien, Denis Garot, Kevin Bouiller, Loïc Epelboin, Stéphane Jauréguiberry, Alexandre Gaymard, Gil Verschelden, Sandra Braz, Joao Miguel Ferreira Ribeiro, Michael Joannidis, Thérèse Staub, Antoine Altdorfer, Richard Greil, Alexander Egle, Jérémie Guedj, Marion Noret, Roberto Roncon-Albuquerque, Jose-Artur Paiva, Bruno Lina, Dominique Costagliola, Yazdan Yazdanpanah, Charles Burdet, France Mentré, Hospices Civils de Lyon (HCL), Université libre de Bruxelles (ULB), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Pôle de Recherche Clinique [Paris] (PRC), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Croix-Rousse [CHU - HCL], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie
Subjects: [SDV]Life Sciences [q-bio]
Abstract: BackgroundThe antiviral efficacy of remdesivir is still controversial. We aimed at evaluating its clinical effectiveness in hospitalised patients with COVID-19, with indication of oxygen and/or ventilator support. Following prior publication of preliminary results, here we present the final results after completion of data monitoring.MethodsIn this European multicentre, open-label, parallel-group, randomised, controlled trial (DisCoVeRy, NCT04315948; EudraCT2020-000936-23), participants were randomly allocated to receive usual standard of care (SoC) alone or in combination with remdesivir, lopinavir/ritonavir, lopinavir/ritonavir and IFN-β-1a, or hydroxychloroquine. Adult patients hospitalised with COVID-19 were eligible if they had clinical evidence of hypoxemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzyme, severe chronic kidney disease, any contra-indication to one of the studied treatments or their use in the 29 days before randomization, or use of ribavirin, as well as pregnancy or breast-feeding. Here, we report results for remdesivir + SoC versus SoC alone. Remdesivir was administered as 200 mg infusion on day 1, followed by once daily infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. Treatment assignation was performed via web-based block randomisation stratified on illness severity and administrative European region. The primary outcome was the clinical status at day 15 measured by the WHO 7-point ordinal scale, assessed in the intention-to-treat population.FindingsBetween March 22nd, 2020 and January 21st, 2021, 857 participants were randomised to one of the two arms in 5 European countries and 843 participants were included for the evaluation of remdesivir (control, n=423; remdesivir, n=420).At day 15, the distribution of the WHO ordinal scale was as follow in the remdesivir and control groups, respectively: Not hospitalized, no limitations on activities: 62/420 (14.8%) and 72/423 (17.0%); Not hospitalized, limitation on activities: 126/420 (30%) and 135/423 (31.9%); Hospitalized, not requiring supplemental oxygen: 56/420 (13.3%) and 31/423 (7.3%); Hospitalized, requiring supplemental oxygen: 75/420 (17.9%) and 65/423 (15.4%); Hospitalized, on non-invasive ventilation or high flow oxygen devices: 16/420 (3.8%) and 16/423 (3.8%); Hospitalized, on invasive mechanical ventilation or ECMO: 64/420 (15.2%) and 80/423 (18.9%); Death: 21/420 (5%) and 24/423 (5.7%). The difference between treatment groups was not statistically significant (OR for remdesivir, 1.02, 95% CI, 0.62 to 1.70, P=0.93). There was no significant difference in the occurrence of Serious Adverse Events between treatment groups (remdesivir, n=147/410, 35.9%, versus control, n=138/423, 32.6%, p=0.29).InterpretationRemdesivir use for the treatment of hospitalised patients with COVID-19 was not associated with clinical improvement at day 15.FundingEuropean Union Commission, French Ministry of Health, DIM One Health Île-de-France, REACTing, Fonds Erasme-COVID-ULB; Belgian Health Care Knowledge Centre (KCE), AGMT gGmbH, FEDER “European Regional Development Fund”, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. Remdesivir was provided free of charge by Gilead.
Published: 2023

4. A homozygous mutation in the human selenocysteine tRNA gene impairs UGA recoding activity and selenoproteome regulation by selenium

Author: Caroline Vindry, Olivia Guillin, Philippe Wolff, Paul Marie, Franck Mortreux, Philippe E Mangeot, Théophile Ohlmann, Laurent Chavatte, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon), Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Abstract: The selenocysteine (Sec) tRNA (tRNA[Ser]Sec) governs Sec insertion into selenoproteins by the recoding of a UGA codon, typically used as a stop codon. A homozygous point mutation (C65G) in the human tRNA[Ser]Sec acceptor arm has been reported by two independent groups and was associated with symptoms such as thyroid dysfunction and low blood selenium levels; however, the extent of altered selenoprotein synthesis resulting from this mutation has yet to be comprehensively investigated. In this study, we used CRISPR/Cas9 technology to engineer homozygous and heterozygous mutant human cells, which we then compared with the parental cell lines. This C65G mutation affected many aspects of tRNA[Ser]Sec integrity and activity. Firstly, the expression level of tRNA[Ser]Sec was significantly reduced due to an altered recruitment of RNA polymerase III at the promoter. Secondly, selenoprotein expression was strongly altered, but, more surprisingly, it was no longer sensitive to selenium supplementation. Mass spectrometry analyses revealed a tRNA isoform with unmodified wobble nucleotide U34 in mutant cells that correlated with reduced UGA recoding activities. Overall, this study demonstrates the pleiotropic effect of a single C65G mutation on both tRNA phenotype and selenoproteome expression.
Published: 2023

5. An integrated, structure- and energy-based view of the genetic code

Author: Henri Grosjean, Eric Westhof, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), and Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Computational biology, Biology, Ribosome, Sense Codon, 03 medical and health sciences, RNA, Transfer, Genetics, Survey and Summary, Codon, chemistry.chemical_classification, [ SDV ] Life Sciences [q-bio], RNA, Genetic code, Amino acid, 030104 developmental biology, chemistry, Genetic Code, Transfer RNA, Nucleic Acid Conformation, Thermodynamics, Ribosomes, GC-content, Decoding methods
Abstract: International audience; The principles of mRNA decoding are conserved among all extant life forms. We present an integrative view of all the interaction networks between mRNA, tRNA and rRNA: the intrinsic stability of codon-anticodon duplex, the conformation of the anticodon hairpin, the presence of modified nucleotides, the occurrence of non-Watson-Crick pairs in the codon-anticodon helix and the interactions with bases of rRNA at the A-site decoding site. We derive a more information-rich, alternative representation of the genetic code, that is circular with an unsymmetrical distribution of codons leading to a clear segregation between GC-rich 4-codon boxes and AU-rich 2:2-codon and 3:1-codon boxes. All tRNA sequence variations can be visualized, within an internal structural and energy framework, for each organism, and each anticodon of the sense codons. The multiplicity and complexity of nucleotide modifications at positions 34 and 37 of the anticodon loop segregate meaningfully, and correlate well with the necessity to stabilize AU-rich codon-anticodon pairs and to avoid miscoding in split codon boxes. The evolution and expansion of the genetic code is viewed as being originally based on GC content with progressive introduction of A/U together with tRNA modifications. The representation we present should help the engineering of the genetic code to include non-natural amino acids.
Published: 2016

6. The 3′UTR‐derived sRNA RsaG coordinates redox homeostasis and metabolism adaptation in response to glucose‐6‐phosphate uptake in Staphylococcus aureus

Author: Alejandro Toledo-Arana, Laura Barrientos, Emma Desgranges, François Vandenesch, Karen Moreau, Stefano Marzi, Pascale Romby, Isabelle Caldelari, Lucas Herrgott, Centre National de la Recherche Scientifique (France), Agence Nationale de la Recherche (France), Université de Strasbourg, Fondation pour la Recherche Médicale, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Instituto de Agrobiotecnología (IdAB), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Romby, Pascale, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and ANR-18-CE12-0025,CoNoCo,Contrôle de la transcription non-codante comme moyen de régulation fine de l'expression des gènes chez les bactéries Bacillus subtilis et Staphylococcus aureus.(2018)
Subjects: Untranslated region, Staphylococcus aureus, Monosaccharide Transport Proteins, [SDV]Life Sciences [q-bio], RNA Stability, Glucose-6-Phosphate, Biology, Microbiology, Antiporters, chemistry.chemical_compound, Bacterial Proteins, Untranslated Regions, Homeostasis, Molecular Biology, Gene, Messenger RNA, Three prime untranslated region, RNA, Biological Transport, Translation (biology), Gene Expression Regulation, Bacterial, Staphylococcal Infections, Adaptation, Physiological, 3′UTR-derived sRNA, Cell biology, [SDV] Life Sciences [q-bio], chemistry, CCPA, Transfer RNA, RNA, Small Untranslated, Oxidation-Reduction, Redox homeostasis, Transcription Factors
Abstract: Staphylococcus aureus RsaG is a 3′-untranslated region (3′UTR) derived sRNA from the conserved uhpT gene encoding a glucose-6-phosphate (G6P) transporter expressed in response to extracellular G6P. The transcript uhpT-RsaG undergoes degradation from 5′- to 3′-end by the action of the exoribonucleases J1/J2, which are blocked by a stable hairpin structure at the 5′-end of RsaG, leading to its accumulation. RsaG together with uhpT is induced when bacteria are internalized into host cells or in the presence of mucus-secreting cells. Using MS2-affinity purification coupled with RNA sequencing, several RNAs were identified as targets including mRNAs encoding the transcriptional factors Rex, CcpA, SarA, and the sRNA RsaI. Our data suggested that RsaG contributes to the control of redox homeostasis and adjusts metabolism to changing environmental conditions. RsaG uses different molecular mechanisms to stabilize, degrade, or repress the translation of its mRNA targets. Although RsaG is conserved only in closely related species, the uhpT 3′UTR of the ape pathogen S. simiae harbors an sRNA, whose sequence is highly different, and which does not respond to G6P levels. Our results hypothesized that the 3′UTRs from UhpT transporter encoding mRNAs could have rapidly evolved to enable adaptation to host niches., This work was supported by the Centre National de la Recherche Scientifique (CNRS), by the French National Research Agency ANR (ANR-18-CE12-0025-04 CoNoCo to P.R.). This work of the Interdisciplinary Thematic Institute IMCBio, as part of the ITI 2021–2028 program of the University of Strasbourg, CNRS, and Inserm was supported by IdEx Unistra (ANR-10-IDEX-0002), SFRI-STRAT'US (ANR 20-SFRI-0012), and by EUR IMCBio (IMCBio ANR-17-EURE-0023) under the framework of the French Investments for the Future Program. ED and LB were supported by the “Fondation pour la Recherche Médicale” (FDT201904007957 and ECO202006011534)
Published: 2021

7. Short-Range Imbalances in the AMBER Lennard-Jones Potential for (Deoxy)Ribose···Nucleobase Lone-Pair···π Contacts in Nucleic Acids

Author: Vojtěch Mlýnský, Jiří Šponer, Holger Kruse, Klaudia Mráziková, Pascal Auffinger, Institute of Biophysics, Czech Academy of Sciences [Prague] (CAS), Department of Physical Chemistry, Faculty of Science-Regional Centre of Advanced Technologies and Materials [Olomouc] (RCPTM)-Palacky University Olomouc, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 010304 chemical physics, Force field (physics), Chemistry, Ribose, General Chemical Engineering, Stacking, General Chemistry, Interaction energy, Molecular Dynamics Simulation, Library and Information Sciences, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Computer Science Applications, Nucleobase, Molecular dynamics, Lennard-Jones potential, Chemical physics, Nucleic Acids, 0103 physical sciences, Quantum Theory, RNA, Density functional theory, Lone pair
Abstract: The lone-pair…π (lp…π) (deoxy)ribose…nucleobase stacking is a recurring structural motif in Z DNA and RNAs that is characterized by sub-van der Waals lp…π contacts (
Published: 2021

8. Phenotypic variability and identification of novel YARS2 mutations in YARS2 mitochondrial myopathy, lactic acidosis and sideroblastic anaemia

Author: Sandra T. Cooper, Minal Menezes, Joëlle Rudinger-Thirion, Lisa G. Riley, Rachael M. Duff, Mark R. Davis, Michel Tchan, Pascale de Lonlay, John Christodoulou, Agnès Rötig, Genetic Metabolic Disorders Research Unit, Westmead Hospital [Sydney]-Kids Research Institute, Discipline of Paediatrics & Child Health, The University of Sydney, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre for Medical Research, The University of Western Australia (UWA)-Western Australian Institute for Medical Research, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genetic Medicine, Westmead Hospital [Sydney], Discipline of Genetic Medicine, Sydney Medical School-The University of Sydney, Diagnostic Genomics, QEII Medical Centre, Institute for Neuroscience and Muscle Research, Kids Research Institute-Westmead Hospital [Sydney], Western Sydney Genetics Program, This research was supported by a March of Dimes Research Grant, and National Health and Medical Research Council of Australia Project Grant 1026891. M.M. is an Australian Mitochondrial Diseases Foundation (AMDF) Postgraduate Research Scholar, and the AMDF also provided financial support to RD and MD., Sydney Medical School, March of Dimes Research Grant, National Health and Medical Research Council of Australia Project Grant 1026891. M.M. is an Australian Mitochondrial Diseases Foundation (AMDF) Postgraduate Research Scholar, and the AMDF also provided financial support to RD and MD., Children's Hospital at Westmead-Kids Research Institute, The University of Sydney [Sydney], Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), The University of Western Australia ( UWA ) -Western Australian Institute for Medical Research, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Westmead Hospital, Children's Hospital at Westmead, BMC, Ed., Architecture et Réactivité de l'ARN, Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ), and Sydney Medical School-The University of Sydney [Sydney]
Subjects: Adult, Mitochondrial respiratory chain, Muscle diseases, Adolescent, Myopathy with lactic acidosis and sideroblastic anemia, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, medicine.disease_cause, DNA, Mitochondrial, Lactic acidaemia, 03 medical and health sciences, Young Adult, Mitochondrial myopathy, Tyrosine-tRNA Ligase, Aminoacyl tRNA-synthetase, medicine, Humans, Genetics(clinical), Pharmacology (medical), Myopathy, Child, Gene, Genetics (clinical), Hydro-Lyases, 030304 developmental biology, Acidosis, Medicine(all), Genetics, 0303 health sciences, Mutation, [SDV.GEN]Life Sciences [q-bio]/Genetics, Research, 030305 genetics & heredity, Infant, Newborn, Infant, General Medicine, Inborn error of metabolism, medicine.disease, Anemia, Sideroblastic, Lactic acidosis, Child, Preschool, Acidosis, Lactic, Female, medicine.symptom, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Mitochondrial myopathies
Abstract: Background Mutations in the mitochondrial tyrosyl-tRNA synthetase (YARS2) gene have previously been identified as a cause of the tissue specific mitochondrial respiratory chain (RC) disorder, Myopathy, Lactic Acidosis, Sideroblastic Anaemia (MLASA). In this study, a cohort of patients with a mitochondrial RC disorder for who anaemia was a feature, were screened for mutations in YARS2. Methods Twelve patients were screened for YARS2 mutations by Sanger sequencing. Clinical data were compared. Functional assays were performed to confirm the pathogenicity of the novel mutations and to investigate tissue specific effects. Results PathogenicYARS2 mutations were identified in three of twelve patients screened. Two patients were found to be homozygous for the previously reported p.Phe52Leu mutation, one severely and one mildly affected. These patients had different mtDNA haplogroups which may contribute to the observed phenotypic variability. A mildly affected patient was a compound heterozygote for two novel YARS2 mutations, p.Gly191Asp and p.Arg360X. The p.Gly191Asp mutation resulted in a 38-fold loss in YARS2 catalytic efficiency and the p.Arg360X mutation did not produce a stable protein. The p.Phe52Leu and p.Gly191Asp/p.Arg360X mutations resulted in more severe RC deficiency of complexes I, III and IV in muscle cells compared to fibroblasts, but had relatively normal YARS2 protein levels. The muscle-specific RC deficiency can be related to the increased requirement for RC complexes in muscle. There was also a failure of mtDNA proliferation upon myogenesis in patient cells which may compound the RC defect. Patient muscle had increased levels of PGC1-α and TFAM suggesting mitochondrial biogenesis was activated as a potential compensatory mechanism. Conclusion In this study we have identified novel YARS2 mutations and noted marked phenotypic variability among YARS2 MLASA patients, with phenotypes ranging from mild to lethal, and we suggest that the background mtDNA haplotype may be contributing to the phenotypic variability. These findings have implications for diagnosis and prognostication of the MLASA and related phenotypes.
Published: 2013

9. Identification of host tRNAs preferentially recognized by the Plasmodium surface protein tRip

Author: Marta Cela, Philippe Wolff, Magali Frugier, Joëlle Rudinger-Thirion, Renaud Geslain, Anne Théobald-Dietrich, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN
Subjects: AcademicSubjects/SCI00010, [SDV]Life Sciences [q-bio], Plasmodium falciparum, Protozoan Proteins, Druggability, Biology, Plasmodium, law.invention, 03 medical and health sciences, 0302 clinical medicine, RNA, Transfer, law, RNA and RNA-protein complexes, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Structural motif, 030304 developmental biology, 0303 health sciences, Membrane Transport Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Translation (biology), biology.organism_classification, Membrane protein, Transfer RNA, Recombinant DNA, Sequence Alignment, human activities, 030217 neurology & neurosurgery, HeLa Cells
Abstract: Malaria is a life-threatening and devastating parasitic disease. Our previous work showed that parasite development requires the import of exogenous transfer RNAs (tRNAs), which represents a novel and unique form of host–pathogen interaction, as well as a potentially druggable target. This import is mediated by tRip (tRNA import protein), a membrane protein located on the parasite surface. tRip displays an extracellular domain homologous to the well-characterized OB-fold tRNA-binding domain, a structural motif known to indiscriminately interact with tRNAs. We used MIST (Microarray Identification of Shifted tRNAs), a previously established in vitro approach, to systematically assess the specificity of complexes between native Homo sapiens tRNAs and recombinant Plasmodium falciparum tRip. We demonstrate that tRip unexpectedly binds to host tRNAs with a wide range of affinities, suggesting that only a small subset of human tRNAs is preferentially imported into the parasite. In particular, we show with in vitro transcribed constructs that tRip does not bind specific tRNAs solely based on their primary sequence, hinting that post-transcriptional modifications modulate the formation of our host/parasite molecular complex. Finally, we discuss the potential utilization of the most efficient tRip ligands for the translation of the parasite's genetic information.
Published: 2021

10. The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins

Author: Rui Xu, Yanyan Lou, Antonin Tidu, Philippe Bulet, Thorsten Heinekamp, Franck Martin, Axel Brakhage, Zi Li, Samuel Liégeois, Dominique Ferrandon, BULET, Philippe, Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sino French Hoffmann Institute, Guangzhou Medical University, Architecture et Réactivité de l'ARN (ARN), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), and Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany]
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], Genetics, Molecular Biology, Biochemistry
Abstract: Host defense against infections encompasses resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, which allows the host to withstand/tolerate pathogens and repair damages. In Drosophila, the Toll signaling pathway is thought to mediate resistance against fungal infections by regulating the secretion of antimicrobial peptides, potentially including Bomanins. We found that Aspergillus fumigatus kills Drosophila Toll pathway mutants without invasion because its dissemination is blocked by melanization, suggesting a role for Toll in host defense distinct from resistance. We report that mutants affecting the Toll pathway or the 55C Bomanin locus were susceptible to the injection of two Aspergillus mycotoxins, restrictocin or verruculogen. The vulnerability of 55C deletion mutants to these mycotoxins was rescued by the overexpression of Bomanins specific to each challenge. Mechanistically, flies in which BomS6 was expressed in the nervous system exhibited an enhanced recovery from the tremors induced by injected verruculogen and displayed improved survival. Thus, innate immunity also protects the host against the action of microbial toxins through secreted peptides and thereby increase its resilience to infection.
Published: 2022

11. The DEAD box RNA helicase DDX42 is an intrinsic inhibitor of positive-strand RNA viruses

Author: Boris Bonaventure, Antoine Rebendenne, Ana Luiza Chaves Valadão, Mary Arnaud‐Arnould, Ségolène Gracias, Francisco Garcia de Gracia, Joe McKellar, Emmanuel Labaronne, Marine Tauziet, Valérie Vivet‐Boudou, Eric Bernard, Laurence Briant, Nathalie Gros, Wassila Djilli, Valérie Courgnaud, Hugues Parrinello, Stéphanie Rialle, Mickaël Blaise, Laurent Lacroix, Marc Lavigne, Jean‐Christophe Paillart, Emiliano P Ricci, Reiner Schulz, Nolwenn Jouvenet, Olivier Moncorgé, Caroline Goujon, Signalisation antivirale - Virus sensing and signaling, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: DEAD-box RNA Helicases, SARS-CoV-2, Genetics, HIV-1, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Virus Replication, Molecular Biology, Biochemistry, Positive-Strand RNA Viruses
Abstract: Genome-wide screens are powerful approaches to unravel regulators of viral infections. Here, a CRISPR screen identifies the RNA helicase DDX42 as an intrinsic antiviral inhibitor of HIV-1. Depletion of endogenous DDX42 increases HIV-1 DNA accumulation and infection in cell lines and primary cells. DDX42 overexpression inhibits HIV-1 infection, whereas expression of a dominant-negative mutant increases infection. Importantly, DDX42 also restricts LINE-1 retrotransposition and infection with other retroviruses and positive-strand RNA viruses, including CHIKV and SARS-CoV-2. However, DDX42 does not impact the replication of several negative-strand RNA viruses, arguing against an unspecific effect on target cells, which is confirmed by RNA-seq analysis. Proximity ligation assays show DDX42 in the vicinity of viral elements, and cross-linking RNA immunoprecipitation confirms a specific interaction of DDX42 with RNAs from sensitive viruses. Moreover, recombinant DDX42 inhibits HIV-1 reverse transcription in vitro. Together, our data strongly suggest a direct mode of action of DDX42 on viral ribonucleoprotein complexes. Our results identify DDX42 as an intrinsic viral inhibitor, opening new perspectives to target the life cycle of numerous RNA viruses.
Published: 2022

12. Comparative study on tertiary contacts and folding of RNase P RNAs from a psychrophilic, a mesophilic/radiation-resistant, and a thermophilic bacterium

Author: Eric Westhof, Andreas Werner, Roland K. Hartmann, Markus Gößringer, Dominik Helmecke, Michal Marszalkowski, Ralph Feltens, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: RNA Folding, RNase P, RNA Stability, Ribonuclease P, Article, 03 medical and health sciences, RNA, Transfer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Psychrophile, Base Pairing, Molecular Biology, 030304 developmental biology, Thermostability, 0303 health sciences, Base Sequence, biology, Thermus thermophilus, 030302 biochemistry & molecular biology, Temperature, RNA, Deinococcus radiodurans, Gene Expression Regulation, Bacterial, biology.organism_classification, Kinetics, Pseudoalteromonas, RNA, Bacterial, Biochemistry, Mutation, Transfer RNA, Thermodynamics, Deinococcus, RNA 3' End Processing, Pseudoknot
Abstract: In most bacterial type A RNase P RNAs (P RNAs), two major loop-helix tertiary contacts (L8–P4 and L18–P8) help to orient the two independently folding S- and C-domains for concerted recognition of precursor tRNA substrates. Here, we analyze the effects of mutations in these tertiary contacts in P RNAs from three different species: (i) the psychrophilic bacterium Pseudoalteromonas translucida (Ptr), (ii) the mesophilic radiation-resistant bacterium Deinococcus radiodurans (Dra), and (iii) the thermophilic bacterium Thermus thermophilus (Tth). We show by UV melting experiments that simultaneous disruption of these two interdomain contacts has a stabilizing effect on all three P RNAs. This can be inferred from reduced RNA unfolding at lower temperatures and a more concerted unfolding at higher temperatures. Thus, when the two domains tightly interact via the tertiary contacts, one domain facilitates structural transitions in the other. P RNA mutants with disrupted interdomain contacts showed severe kinetic defects that were most pronounced upon simultaneous disruption of the L8–P4 and L18–P8 contacts. At 37°C, the mildest effects were observed for the thermostable Tth RNA. A third interdomain contact, L9–P1, makes only a minor contribution to P RNA tertiary folding. Furthermore, D. radiodurans RNase P RNA forms an additional pseudoknot structure between the P9 and P12 of its S-domain. This interaction was found to be particularly crucial for RNase P holoenzyme activity at near-physiological Mg2+ concentrations (2 mM). We further analyzed an exceptionally stable folding trap of the G,C-rich Tth P RNA.
Published: 2021

13. Revisiting the JOQUER trial: stratification of primary Sjögren’s syndrome and the clinical and interferon response to hydroxychloroquine

Author: Dennis Lendrem, Iris L A Bodewes, Nadia Howard-Tripp, Jessica Tarn, Marjan A. Versnel, Alexis Collins, Raphaèle Seror, Jacques-Eric Gottenberg, Xavier Mariette, James Wason, Wan-Fai Ng, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Erasmus University Medical Center [Rotterdam] (Erasmus MC), CHU Strasbourg, Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, seror, raphaele, and Immunology
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Placebo, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Interferon, Internal medicine, medicine, Immunology and Allergy, Clinical Trials, 030212 general & internal medicine, Depression (differential diagnoses), 030203 arthritis & rheumatology, business.industry, Repeated measures design, Hydroxychloroquine, [SDV] Life Sciences [q-bio], Sjögren’s syndrome, Anxiety, Sjögren's syndrome, Sjogren s, medicine.symptom, business, medicine.drug
Abstract: To re-analyse the clinical outcomes and interferon (IFN) activity data from the JOQUER trial, a phase III trial investigating hydroxychloroquine (HCQ) in patients with primary Sjögren’s syndrome (pSS), after stratifying patients into putative pathobiological subgroups utilizing the Newcastle Sjögren’s Stratification Tool (NSST) based on patient-reported symptoms of dryness, pain, fatigue, anxiety and depression. 107 patients were assigned to one of four subgroups using NSST at baseline—the high symptom burden (HSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and low symptom burden (LSB). Endpoints were re-analysed after stratification, testing for treatment differences within subgroups and adjusting for baseline differences using a repeated measures covariate model. The HSB subgroup (n = 32) showed a relative improvement in ESSPRI of 1.49 points (95% CI 0.54–2.43; p = 0.002) within 12 weeks in patients taking HCQ compared to placebo, with no further changes after 24 weeks. For the LSB subgroup (n = 14), the ESSPRI worsened in the placebo but not the HCQ arm after 12 weeks (mean difference 1.44, 95% CI 0.05–2.83, p = 0.042). Neither the HSB nor the LSB patients showed significant changes in IFN activity at 24 weeks. There were no significant differences in ESSPRI in the PDF (n = 39) and DDF (n = 22) patients taking HCQ. However, significant reductions in overall IFN score at 24 weeks were seen in both PDF (difference at 24 weeks; 6.41, 95% CI, 2.48–10.34, p = 0.002) and DDF (difference at 24 weeks; 7.23, 95% CI, 1.85–12.6, p = 0.009) without improvement in ESSPRI. Although the JOQUER trial reported no overall benefit from HCQ in pSS patients, stratification suggests that both HSB and LSB subgroups may respond to HCQ. However, these patients may benefit through mechanisms other than the reduction of IFN activities.
Published: 2021

14. Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a mediator of infantile encephalopathy

Author: Michael Fähling, Josué Feingold, Edgar Benko, Marc Bintner, Diana Rodriguez, Simonetta Bandiera, Sylvain Hanein, Patrick Munier, Pascale Krejbich-Trotot, Stanislas Lyonnet, Jeanine Vellayoudom, Arnold Munnich, Eric Westhof, Nathalie Boddaert, Alexandra Henrion-Caude, Muriel Girard, Michel Renouil, Magali Naville, Jean-Jacques Hoarau, Emmanuelle Génin, Isabelle Desguerre, Pascale de Lonlay, François Cartault, Alain Fourmaintraux, Service de génétique, Centre hospitalier Felix Guyon (Saint-Denis), Service de Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe de Recherche en Immunopathologies et maladies infectueuses ( GRI ), Université de la Réunion ( UR ) -Centre hospitalier Régional Site Félix Guyon, Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), Cités, Territoires, Environnement et Sociétés ( CITERES ), Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Variabilité Génétique et Maladies Humaines, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Groupe Hospitalier Sud Réunion ( GHSR ), CHR La réunion, Institut de génétique et microbiologie [Orsay] ( IGM ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Référence Maladies Rares ' malformations et maladies congénitales du cervelet ', Hospices Civils de Lyon ( HCL ) -CHU Trousseau [APHP]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de neuropédiatrie [Trousseau], Service de Génétique Médicale [CHU Necker], Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Cités, Territoires, Environnement et Sociétés (CITERES), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe Hospitalier Sud Réunion (GHSR), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Tours (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours
Subjects: RNA, Untranslated, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Retrotransposon, 0302 clinical medicine, Chromosome Segregation, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Indian Ocean, Conserved Sequence, Genetics, 0303 health sciences, Brain Diseases, Multidisciplinary, Geography, Nucleotides, Chromosome Mapping, Biological Sciences, Non-coding RNA, Magnetic Resonance Imaging, Anorexia, Phenotype, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease Progression, medulla oblongata, Chromosomes, Human, Pair 8, Primates, Retroelements, pediatrics, Molecular Sequence Data, Genes, Recessive, Biology, 03 medical and health sciences, Young Adult, genetic disease, Animals, Humans, long noncoding RNA, Gene, 030304 developmental biology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Base Sequence, Point mutation, Intron, RNA, Infant, long interspersed element 1, Noncoding DNA, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genetic Loci, Mutation, Nucleic Acid Conformation, Human genome, 030217 neurology & neurosurgery
Abstract: International audience; The human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recognized, the significance of subtle variations in their sequence remains mostly unexplored. Here we report homozygosity mapping of an infantile neurodegenerative disease locus in a genetic isolate. Complete DNA sequencing of the 400-kb linkage locus revealed a point mutation in a primate-specific retrotransposon that was transcribed as part of a unique noncoding RNA, which was expressed in the brain. In vitro knockdown of this RNA increased neuronal apoptosis, consistent with the inappropriate dosage of this RNA in vivo and with the phenotype. Moreover, structural analysis of the sequence revealed a small RNA-like hairpin that was consistent with the putative gain of a functional site when mutated. We show here that a mutation in a unique transposable element-containing RNA is associated with lethal encephalopathy, and we suggest that RNAs that harbor evolutionarily recent repetitive elements may play important roles in human brain development.
Published: 2012

15. Satellite cell loss and impaired muscle regeneration in selenoprotein N deficiency

Author: Valérie Allamand, Pascale Guicheney, Mathieu Rederstorff, Alain Lescure, Maud Beuvin, Guillaume Chazot, Norma B. Romero, Marie Castets, Fabien Le Grand, Arnaud Ferry, Alain Krol, Anne Bertrand, Perrine Castets, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Biocenter, Section for Genomics and RNomics, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Innsbruck Medical University [Austria] (IMU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Werling, Danièle, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Innsbruck Medical University [Austria] ( IMU ), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Pitié-Salpêtrière [APHP], University of Basel (Unibas), Centre de recherche Médecine, Science, Santé et Société (CERMES), Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), U974, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]
Subjects: Programmed cell death, Satellite Cells, Skeletal Muscle, Cell Survival, Population, Cobra Cardiotoxin Proteins, Endogeny, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Muscular Diseases, Genetics, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Regeneration, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Myopathy, education, Muscle, Skeletal, Selenoproteins, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics (clinical), Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, Mice, Knockout, 0303 health sciences, education.field_of_study, Selenoprotein N, Ryanodine receptor, Regeneration (biology), General Medicine, Anatomy, Cell biology, Disease Models, Animal, Mutation, medicine.symptom, 030217 neurology & neurosurgery, Homeostasis
Abstract: International audience; Selenoprotein N (SelN) deficiency causes a group of inherited neuromuscular disorders termed SEPN1-related myopathies (SEPN1-RM). Although the function of SelN remains unknown, recent data demonstrated that it is dispensable for mouse embryogenesis and suggested its involvement in the regulation of ryanodine receptors and/or cellular redox homeostasis. Here, we investigate the role of SelN in satellite cell (SC) function and muscle regeneration, using the Sepn1(-/-) mouse model. Following cardiotoxin-induced injury, SelN expression was strongly up-regulated in wild-type muscles and, for the first time, we detected its endogenous expression in a subset of mononucleated cells by immunohistochemistry. We show that SelN deficiency results in a reduced basal SC pool in adult skeletal muscles and in an imperfect muscle restoration following a single injury. A dramatic depletion of the SC pool was detected after the first round of degeneration and regeneration that totally prevented subsequent regeneration of Sepn1(-/-) muscles. We demonstrate that SelN deficiency affects SC dynamics on isolated single fibres and increases the proliferation of Sepn1(-/-) muscle precursors in vivo and in vitro. Most importantly, exhaustion of the SC population was specifically identified in muscle biopsies from patients with mutations in the SEPN1 gene. In conclusion, we describe for the first time a major physiological function of SelN in skeletal muscles, as a key regulator of SC function, which likely plays a central role in the pathophysiological mechanism leading to SEPN1-RM.
Published: 2011

16. Neutrophils degranulate GAG-containing proteoglycofili, which block Shigella growth and degrade virulence factors

Author: Antonin C André, Marina Valente Barroso, Jurate Skerniskyte, Mélina Siegwald, Vanessa Paul, Lorine Debande, Caroline Ridley, Isabelle Svahn, Stéphane Rigaud, Jean-Yves Tinevez, Romain R Vivès, Philippe J Sansonetti, David J Thornton, Benoit S Marteyn, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), University of Manchester [Manchester], Bordeaux Imaging Center (BIC), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagopole (CITECH), Institut Pasteur [Paris] (IP), CEA Grenoble (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Tinevez, Jean-Yves
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: Summary paragraphNeutrophil degranulation plays a central role in their ability to kill pathogens but also to stimulate other immune cells1–3. Here we show that neutrophil degranulation, induced in hypoxia or upon Shigella infection in vitro and in vivo, leads to the release of polymers called neutrophil Proteoglycofili (PGF). PGF are mainly composed of granular proteins (myeloperoxidase, elastase, lactoferrin, cathelicidin, albumin) pre-stored in various types of granules, and chondroitin sulfate. PGF individual fibers have a diameter of 43.9 ± 20.3 nm and. They secreted by viable neutrophils and do not contain DNA, as opposed to NETs which contains also granular proteins, chondroitin sulfate in addition to chromatin, released upon neutrophil disintegration and cell death.We demonstrated that PGF block the growth of Shigella and other bacteria and degrade Shigella virulence factors. The degradation of the chondroitin sulfate polymers with testes hyaluronidases destabilizes PGF ultrastructure and abolishes its antimicrobial activity. Our results provide novel insights in the neutrophil degranulation process and open new doors for the investigation of PGF contribution to cytokines concentration gradient formation and adaptive immune cells activation. Further investigations are required to better appreciate the importance of this “sterile blaster” in infectious or inflammatory diseases.
Published: 2022

17. Phytobeneficial traits of rhizobacteria under the control of multiple molecular dialogues

Author: Arnaud Laveilhé, Sylvain Fochesato, David Lalaouna, Thierry Heulin, Wafa Achouak, Laboratoire d'Ecologie Microbienne de la Rhizosphère et d'Environnements Extrêmes (LEMIRE), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Bacteria, Iron, Rhizosphere, Fungi, food and beverages, Bioengineering, Applied Microbiology and Biotechnology, Biochemistry, Soil Microbiology, Biotechnology, Alphaproteobacteria, Plant Diseases
Abstract: International audience; Pseudomonads play crucial roles in plant growth promotion and control of plant diseases. However, under natural conditions, other microorganisms competing for the same nutrient resources in the rhizosphere may exert negative control over their phytobeneficial characteristics. We assessed the expression of phytobeneficial genes involved in biocontrol, biostimulation and iron regulation such as, phlD, hcnA, acdS, and iron-small regulatory RNAs prrF1 and prrF2 in Pseudomonas brassicacearum co-cultivated with three phytopathogenic fungi, and two rhizobacteria in the presence or absence of Brassica napus, and in relation to iron availability. We found that the antifungal activity of P. brassicacearum depends mostly on the production of DAPG and not on HCN whose production is suppressed by fungi. We have also shown that the twocompeting bacterial strains modulate the plant growth promotion activity of P. brassicacearum by modifying the expression of phlD, hcnA and acdS according to iron availability. Overall, it allows us to better understand the complexity of the multiple molecular dialogues that take place underground between microorganisms and between plants and its rhizosphere microbiota and to show that synergy in favour of phytobeneficial gene expression may exist between different bacterial species.
Published: 2022

18. In vitro characterization of naturally occurring influenza H3NA- viruses lacking the NA gene segment: toward a new mechanism of viral resistance?

Author: E. Fournier, Daniel Thomas, Matthieu Yver, C. Boule, Vincent Moules, Emmanuel Giudice, Manuel Rosa-Calatrava, Bruno Lina, Corinne Bergeron, Roland Marquet, Nadia Naffakh, Guy Schoehn, Yi Pu Lin, Alan Hay, Martine Valette, Aurélien Traversier, Olivier Ferraris, A. Rivoire, M. Bouscambert-Duchamp, Michèle Ottmann, Jean-Paul Rolland, Olivier Terrier, Virologie et Pathologie Humaine ( VirPath ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions cellulaires et moléculaires ( ICM ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique moléculaire des virus à ARN, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Virologie et Pathologie Humaine (VirPath), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires et moléculaires (ICM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, viral resistance, Protein Conformation, viruses, neuraminidase, medicine.disease_cause, Virus Replication, Influenza A virus, Enzyme Inhibitors, chemistry.chemical_classification, 0303 health sciences, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], virus diseases, Orthomyxoviridae, 3. Good health, influenza, Gene Expression Regulation, Viral, Hemagglutinin (influenza), Antiviral Agents, Gene Expression Regulation, Enzymologic, Cell Line, 03 medical and health sciences, Dogs, Oseltamivir, Virology, Drug Resistance, Viral, medicine, Animals, Humans, Amino Acid Sequence, hemagglutinin, Gene, 030304 developmental biology, 030306 microbiology, Influenza A Virus, H3N2 Subtype, Cryoelectron Microscopy, Virion, biology.organism_classification, Reverse genetics, Viral replication, chemistry, biology.protein, cryo-EM, Glycoprotein, Neuraminidase, Sequence Alignment, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]
Abstract: International audience; Among a panel of 788 clinical influenza H3N2 isolates, two isolates were characterized by an oseltamivir-resistant phenotype linked to the absence of any detectable NA activity. Here, we established that the two H3NA- isolates lack any detectable full-length NA segment, and one of these could be rescued by reverse genetics in the absence of any NA segment sequence. We found that the absence of NA segment induced a moderate growth defect of the H3NA- viruses as on cultured cells. The glycoproteins density at the surface of H3NA- virions was unchanged as compared to H3N2 virions. The HA protein as well as residues 188 and 617 of the PB1 protein were shown to be strong determinants of the ability of H3NA- viruses to grow in the absence of the NA segment. The significance of these findings about naturally occurring seven-segment influenza A viruses is discussed.
Published: 2010

19. A multi-laboratory benchmark study of isothermal titration calorimetry (ITC) using Ca2+ and Mg2+ binding to EDTA

Author: Huaying Zhao, Adrián Velázquez-Campoy, Di Wu, Eric Ennifar, Shih Chia Tso, Jonas Höring, Louis Bourlon, Grzegorz Piszczek, Chad A. Brautigam, Olga Abian, Sandro Keller, Patrick England, Rafael Claveria-Gimeno, Bárbara Claro, Jonathan B. Chaires, Margarida Bastos, Peter Schuck, Fundação para a Ciência e a Tecnologia (Portugal), Ministerio de Economía y Competitividad (España), Ministerio de Educación y Cultura (España), Instituto de Salud Carlos III, European Commission, Diputación General de Aragón, Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (España), National Institutes of Health (US), National Institute of Biomedical Imaging and Bioengineering (US), Ministério da Saúde (Portugal), Universidade do Porto (Portugal), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Fundación Agencia Aragonesa para la Investigación y el Desarrollo (ARAID), Universidade do Porto, Instituto Aragonés de Ciencias de la Salud [Zaragoza] (IACS), Technische Universität Kaiserslautern (TU Kaiserslautern), Biophysique Moléculaire (plateforme) - Molecular Biophysics (platform), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Louisville, National Institutes of Health [Bethesda] (NIH), University of Texas Southwestern Medical Center [Dallas], Karl-Franzens-Universität [Graz, Autriche], BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität [Graz, Autriche]-Medical University Graz, M.B. acknowledges the financial support from Fundação para a Ciência e Tecnologia (FCT), Portugal, together with FEDER through 'Programa Operacional Competitividade e Internacionalização' (POCI), by COMPETE2020 to Projects POCI-01-0145-FEDER-030579 and UIDB/00081/2020. A.V.C. and O.A. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2013-47064-P and BFU2016-78232-P to A.V.C.), the Spanish Ministry of Education and Culture (FPU13/3870 to R.C.G.), Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and European Union (ERDF/ESF, 'Investing in your future') (PI15/00663 and PI18/00349 to O.A.), Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_20R to A.V.C. and Digestive Pathology Group B25_20R to O.A.) and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). JBC was supported by NIH Grant GM077422. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. MB gratefully acknowledges the support of Frederico Silva of the Biochemical and Biophysical Technologies Scientific Platform of the Instituto de Investigação e Inovação em Saúde, I3S, Universidade do Porto. We all thank COST Action CA15126, Working Group 4, for the support to this study., Universidade do Porto = University of Porto, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Karl-Franzens-Universität Graz, Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, University of Graz, and Graz University of Technology [Graz] (TU Graz)-University of Graz-Medical University Graz
Subjects: 0301 basic medicine, 030103 biophysics, Data treatment, Sample preparation, Biophysics, Standard reaction, computer.software_genre, Isothermal Titration Calorimetry (ITC), Standard deviation, Set (abstract data type), 03 medical and health sciences, Software, Benchmark study, Ligand-binding, Mathematics, Protocol (science), business.industry, Isothermal titration calorimetry, General Medicine, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 030104 developmental biology, Benchmark (computing), Data mining, business, computer
Abstract: 23 pags., 11 figs., 14 tabs., A small-scale ITC benchmarking study was performed involving 9 biophysics laboratories/facilities, to evaluate inter-laboratory and intra-laboratory basal levels of uncertainty. Our prime goal was to assess a number of important factors that can influence both the data gathered by this technique and the thermodynamic parameter values derived therefrom. In its first part, the study involved 5 laboratories and 13 different instruments, working with centrally prepared samples and the same experimental protocol. The second part involved 4 additional laboratories and 6 more instruments, where the users prepared their own samples according to provided instructions and did the experiments following the same protocol as in the first part. The study design comprised: (1) selecting a minimal set of laboratories; (2) providing very stable samples; (3) providing samples not requiring preparation or manipulation; and (4) providing a well-defined and detailed experimental protocol. Thus, we were able to assess: (i) the variability due to instrument and data analysis performed by each user on centrally prepared samples; (ii) the comparability of data retrieved when using 4 different software packages to analyze the same data, besides the data analysis carried out by the different users on their own experimental results; and (iii) the variability due to local sample preparation (second part of the study). Individual values, as well as averages and standard deviations for the binding parameters for EDTA-cation interaction, were used as metrics for comparing the equilibrium association constant (logK), enthalpy of interaction (ΔH), and the so-called “stoichiometry” (n), a concentration-correction factor., M.B. acknowledges the fnancial support from Fundação para a Ciência e Tecnologia (FCT), Portugal, together with FEDER through “Programa Operacional Competitividade e Internacionalização” (POCI), by COMPETE2020 to Projects POCI-01-0145- FEDER-030579 and UIDB/00081/2020. A.V.C. and O.A. acknowledge fnancial support from the Spanish Ministry of Economy and Competitiveness and European ERDF Funds (MCIU/AEI/FEDER, EU) (BFU2013-47064-P and BFU2016-78232-P to A.V.C.), the Spanish Ministry of Education and Culture (FPU13/3870 to R.C.G.), Fondo de Investigaciones Sanitarias from Instituto de Salud Carlos III and European Union (ERDF/ESF, “Investing in your future”) (PI15/00663 and PI18/00349 to O.A.), Diputación General de Aragón (Protein Targets and Bioactive Compounds Group E45_20R to A.V.C. and Digestive Pathology Group B25_20R to O.A.) and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). JBC was supported by NIH Grant GM077422. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. MB gratefully acknowledges the support of Frederico Silva of the Biochemical and Biophysical Technologies Scientifc Platform of the Instituto de Investigação e Inovação em Saúde, I3S, Universidade do Porto. We all thank COST Action CA15126, Working Group 4, for the support to this study
Published: 2021

20. A purine loop and the primer binding site are critical for the selective encapsidation of mouse mammary tumor virus genomic RNA by Pr77Gag

Author: Lizna M. Ali, Fathima Nuzra Nagoor Pitchai, Serena Bernacchi, Tahir A. Rizvi, Valérie Vivet-Boudou, Roland Marquet, Vineeta N. Pillai, Akhil Chameettachal, Farah Mustafa, Anjana Krishnan, United Arab Emirates University (UAEU), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: AcademicSubjects/SCI00010, RNA Splicing, Gene Products, gag, Genome, Viral, Biology, Vectors in gene therapy, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, Mice, Genetics, RNA and RNA-protein complexes, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Guide RNA, Binding site, 030304 developmental biology, DNA Primers, 0303 health sciences, Binding Sites, Virus Assembly, 030302 biochemistry & molecular biology, Mouse mammary tumor virus, RNA, Group-specific antigen, biology.organism_classification, Footprinting, Dynamic Light Scattering, 3. Good health, Cell biology, Mammary Tumor Virus, Mouse, Purines, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Nucleic Acid Conformation, RNA, Viral, Primer binding site
Abstract: Retroviral RNA genome (gRNA) harbors cis-acting sequences that facilitate its specific packaging from a pool of other viral and cellular RNAs by binding with high-affinity to the viral Gag protein during virus assembly. However, the molecular intricacies involved during selective gRNA packaging are poorly understood. Binding and footprinting assays on mouse mammary tumor virus (MMTV) gRNA with purified Pr77Gag along with in cell gRNA packaging study identified two Pr77Gag binding sites constituting critical, non-redundant packaging signals. These included: a purine loop in a bifurcated stem-loop containing the gRNA dimerization initiation site, and the primer binding site (PBS). Despite these sites being present on both unspliced and spliced RNAs, Pr77Gag specifically bound to unspliced RNA, since only that could adopt the native bifurcated stem–loop structure containing looped purines. These results map minimum structural elements required to initiate MMTV gRNA packaging, distinguishing features that are conserved amongst divergent retroviruses from those perhaps unique to MMTV. Unlike purine-rich motifs frequently associated with packaging signals, direct involvement of PBS in gRNA packaging has not been documented in retroviruses. These results enhance our understanding of retroviral gRNA packaging/assembly, making it not only a target for novel therapeutic interventions, but also development of safer gene therapy vectors., Graphical Abstract Graphical AbstractA single stranded purines (ssPurine) loop in a bifurcated stem-loop structure containing the genomic RNA dimerization initiation site (DIS) hairpin, and the primer binding site (PBS) play a crucial role in the packaging of MMTV genomic RNA by recruiting Pr77Gag precursor polyprotein.
Published: 2021

21. Transfer RNA Recognition and Aminoacylation by Synthetases

Author: Giegé, Richard, Eriani, Gilbert, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, protein synthesis, [SDV]Life Sciences [q-bio], translation, identity antideterminant, genetic code, 03 medical and health sciences, 0302 clinical medicine, RNA recognition, aminoacyl-tRNA synthetase, tRNA post-transcriptional modification, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Allostery, identity determinants, tRNA, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: International audience; Fidelity of transfer ribonucleic acid (tRNA) charging by amino acids ensures correct translation of the genetic code into proteins. Charging is catalysed by a set of enzymes known as aminoacyl-tRNA synthetases. Owing to the degeneracy of the genetic code, some of the different tRNAs have the same amino acid attached to them. Specificity of charging obeys universal rules and is ensured by positive elements, the identity determinants unique to each tRNA and responsible for its recognition by the cognate synthetase, and negative elements, the antideterminants that prevent false recognitions. To fulfil the aminoacylation specificity and prevent noncognate aminoacyl-tRNA delivery to the ribosome, some synthetases also mediate proofreading reactions that increase fidelity of the tRNA charging. In such reactions, misactivated amino acids or mischarged tRNAs are checked in specific sites and noncognate products are hydrolysed. However, mischarging is beneficial under certain stress circumstances or when catalysed by nondiscriminatory synthetases, and represents a driving force in evolution. Key Concepts: •Translational expression of the genetic code refers to aminoacyl-tRNA-and ribosomedependent decoding of genes into proteins, a process highly dependent on fidelity of tRNA aminoacylation by synthetases. •The rules that account for the aminoacylation identity of tRNAs are referred to as the second genetic code. •The RNA operational code is encoded in the acceptor stem of tRNA and is crucial for recognition by aminoacyl-tRNA synthetases and specific aminoacylation. •Allostery in tRNA-synthetase systems concerns long-range transfer of chemical information (up to 75 Å) to the synthetase catalytic site (through the body of tRNA and/or synthetase) triggered by contacts of tRNA identity determinants with the synthetase. •Engineering the identity of tRNA-synthetase systems allows reprogramming the genetic code.
Published: 2021

22. Probing mRNA structure and sRNA-mRNA interactions in bacteria using enzymes and lead(II)

Author: Chevalier, Clément, Geissmann, Thomas, Helfer, Anne-Catherine, Romby, Pascale, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), and Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Staphylococcus aureus, RNA, Untranslated, MESH : RNA, Messenger, MESH : RNA, Untranslated, MESH : Molecular Sequence Data, Molecular Sequence Data, MESH : Nucleic Acid Conformation, MESH: Enzymes, MESH : Enzymes, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Chemical Fractionation, MESH: Base Sequence, MESH: RNA, Untranslated, MESH: Chemical Fractionation, MESH : Hydrolysis, MESH: RNA, MESH : RNA, MESH: Staphylococcus aureus, RNA, Messenger, Molecular Biology, MESH: RNA, Messenger, MESH: Molecular Sequence Data, Base Sequence, MESH : Chemical Fractionation, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Hydrolysis, MESH : Staphylococcus aureus, MESH: Molecular Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Molecular Biology, MESH : RNA, Bacterial, Enzymes, RNA, Bacterial, MESH: Nucleic Acid Conformation, Lead, Nucleic Acid Conformation, RNA, MESH : Base Sequence, MESH : Lead, MESH: RNA, Bacterial, MESH: Hydrolysis, MESH: Lead
Abstract: International audience; Enzymatic probing and lead(II)-induced cleavages have been developed to study the secondary structure of RNA molecules either free or engaged in complex with different ligands. Using a combination of probes with different specificities (unpaired vs. paired regions), it is possible to get information on the accessibility of each nucleotide, on the binding site of a ligand (noncoding RNAs, protein, metabolites), and on RNA conformational changes that accompanied ligand binding or environmental conditions (temperature, pH, ions, etc.). The detection of the cleavages can be conducted by two different ways, which are chosen according to the length of the studied RNA. The first method uses end-labeled RNA molecules and the second one involves primer extension by reverse transcriptase. We provide here an experimental procedure that was designed to map the structure of mRNA and mRNA-sRNA interaction in vitro.
Published: 2009

23. HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells

Author: Julie Lemay, Richard Benarous, Jean-Christophe Rain, Eric Ennifar, Lang Xia Liu, Priscilla Maidou-Peindara, Thomas Bader, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AB Science, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Hybrigenics [Paris], Hybrigenics, CellVir, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Architecture et Réactivité de l'ARN ( ARN ), Institut de biologie moléculaire et cellulaire ( IBMC ), and Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Strasbourg ( UNISTRA ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Cell Line, Fluoroimmunoassay, RNA-binding protein, MESH : RNA, Small Interfering, Virus Replication, MESH: Fluoroimmunoassay, ELAV-Like Protein 1, MESH: HIV-1, MESH : Protein Interaction Mapping, Protein Interaction Mapping, MESH: RNA, Small Interfering, MESH : HIV Reverse Transcriptase, MESH: Gene Silencing, RNA, Small Interfering, MESH: Chromatin Immunoprecipitation, 0303 health sciences, 030302 biochemistry & molecular biology, RNA-Binding Proteins, HIV Reverse Transcriptase, 3. Good health, MESH : Virus Replication, Infectious Diseases, ELAV Proteins, MESH: RNA, Viral, Antigens, Surface, RNA, Viral, RIP-Chip, MESH : Antigens, Surface, MESH : HIV-1, Binding domain, lcsh:Immunologic diseases. Allergy, Chromatin Immunoprecipitation, MESH : Fluoroimmunoassay, MESH: Antigens, Surface, MESH: HIV Reverse Transcriptase, MESH : RNA-Binding Proteins, Biology, MESH: Two-Hybrid System Techniques, Cell Line, 03 medical and health sciences, MESH : Chromatin Immunoprecipitation, Virology, Two-Hybrid System Techniques, MESH : Gene Silencing, MESH : RNA, Viral, Humans, Protein Interaction Domains and Motifs, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, RNase H, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Protein Interaction Domains and Motifs, Binding Sites, MESH: Humans, Research, MESH : Humans, MESH: Protein Interaction Mapping, MESH: Virus Replication, RNA, Molecular biology, Reverse transcriptase, MESH: Cell Line, MESH: RNA-Binding Proteins, Viral replication, MESH : Two-Hybrid System Techniques, MESH: Binding Sites, biology.protein, HIV-1, lcsh:RC581-607, Chromatin immunoprecipitation, MESH : Binding Sites, MESH : Protein Interaction Domains and Motifs
Abstract: Reverse transcription of the genetic material of human immunodeficiency virus type 1 (HIV-1) is a critical step in the replication cycle of this virus. This process, catalyzed by reverse transcriptase (RT), is well characterized at the biochemical level. However, in infected cells, reverse transcription occurs in a multiprotein complex – the reverse transcription complex (RTC) – consisting of viral genomic RNA associated with viral proteins (including RT) and, presumably, as yet uncharacterized cellular proteins. Very little is known about the cellular proteins interacting with the RTC, and with reverse transcriptase in particular. We report here that HIV-1 reverse transcription is affected by the levels of a nucleocytoplasmic shuttling protein – the RNA-binding protein HuR. A direct protein-protein interaction between RT and HuR was observed in a yeast two-hybrid screen and confirmed in vitro by homogenous time-resolved fluorescence (HTRF). We mapped the domain interacting with HuR to the RNAse H domain of RT, and the binding domain for RT to the C-terminus of HuR, partially overlapping the third RRM RNA-binding domain of HuR. HuR silencing with specific siRNAs greatly impaired early and late steps of reverse transcription, significantly inhibiting HIV-1 infection. Moreover, by mutagenesis and immunoprecipitation studies, we could not detect the binding of HuR to the viral RNA. These results suggest that HuR may be involved in and may modulate the reverse transcription reaction of HIV-1, by an as yet unknown mechanism involving a protein-protein interaction with HIV-1 RT.
Published: 2008

24. Reaction between Graphene Oxide and Intracellular Glutathione Affects Cell Viability and Proliferation

Author: Baojin Ma, Alberto Bianco, Yuta Nishina, Shi Guo, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Materials science, oxidation, Cell Survival, reduction, Biocompatible Materials, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Oxidative phosphorylation, medicine.disease_cause, ACS Applied Materials & Interfaces Manuscript ID am-2020-17523u.R2 carbon nanomaterial, Cell Line, chemistry.chemical_compound, medicine, Humans, General Materials Science, Viability assay, Cytotoxicity, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, chemistry.chemical_classification, Reactive oxygen species, Cell growth, Glutathione, Cell biology, Oxidative Stress, chemistry, cancer cells, Graphite, Chimie/Chimie thérapeutique, Reactive Oxygen Species, Intracellular, Oxidative stress, HeLa Cells
Abstract: Graphene oxide (GO) is currently developed for biomedical applications as a promising nanoplatform for drug delivery, phototherapy, and biosensing. As a consequence, its safety and cytotoxicity issues have attracted extensive attention. It has been demonstrated that GO causes an increase of intracellular oxidative stress, likely leading to its cytotoxicity and inhibition of cell proliferation. Being one of the main reductive intracellular substances, glutathione (GSH) is vital in the regulation of the oxidative stress level to maintain normal cellular functions. In this study, we found that GSH could be oxidized to GSSG by GO, leading to the formation of reduced GO (rGO). GSH depletion affects the intracellular reductive/oxidative balance, provoking the increase of the reactive oxygen species level, sequentially inhibiting cell viability and proliferation. Therefore, the reaction between GO and GSH provides a new perspective to explain the origin of GO cytotoxicity.
Published: 2021

25. Deflating the RNA Mg2+ bubble: stereochemistry to the rescue!

Author: Pascal Auffinger, Eric Ennifar, Luigi D'Ascenzo, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, University of California, The Scripps Research Institute [La Jolla], University of California [San Diego] (UC San Diego), and University of California-University of California
Subjects: Cryo-electron microscopy, Stereochemistry, Bubble, Ionic bonding, Biology, 010402 general chemistry, 01 natural sciences, Ribosome, Divalent, Ion, 03 medical and health sciences, Ion binding, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Ionic atmosphere, 030302 biochemistry & molecular biology, RNA, Ribosomal RNA, 0104 chemical sciences, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Solvation shell, Chemical physics
Abstract: Proper evaluation of the ionic structure of biomolecular systems remains challenging in X ray and cryo-EM techniques but is essential for advancing our understanding of complex structure/activity/solvent relationships. However, numerous studies overestimate the number of MgProper evaluation of the ionic structure of biomolecular systems remains challenging in X ray and cryo-EM techniques but is essential for advancing our understanding of complex structure/activity/solvent relationships. However, numerous studies overestimate the number of Mg2+ in the deposited structures and underrate the importance of stereochemical rules to correctly assign these ions. Herein, we re-evaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure and establish that stereochemical principles need consideration when evaluating ion binding features, even when K+ anomalous signals are available as it is the case for 6QNR. Assignment errors can result in misleading conceptions of the solvent structure of ribosomes and other RNA systems and should therefore be avoided. Our analysis resulted in a significant decrease of the number of bound Mg2+ in the 6QNR structure, suggesting that K+ and not Mg2+ is the prevalent ion in the ribosome 1st solvation shell. We stress that the use of proper stereochemical guidelines is critical for deflating the current Mg2+ bubble witnessed in many ribosome and other RNA structures. Herewith, we would like to draw the attention of the researchers interested in the ionic structure of biomolecular systems on the importance and complementarity of stereochemistry and other ion identification techniques such as those pertaining to the detection of anomalous signals of transition metals and K+ We also stress that for the identification of lighter ions such as Mg2+, Na+, , stereochemistry coupled with high resolution structures remain the best currently available option. in the deposited structures and underrate the importance of stereochemical rules to correctly assign these ions. Herein, we re-evaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure and establish that stereochemical principles need consideration when evaluating ion binding features, even when K+ anomalous signals are available as it is the case for 6QNR. Assignment errors can result in misleading conceptions of the solvent structure of ribosomes and other RNA systems and should therefore be avoided. Our analysis resulted in a significant decrease of the number of bound Mg2+ in the 6QNR structure, suggesting that K+ and not Mg2+ is the prevalent ion in the ribosome 1st solvation shell. We stress that the use of proper stereochemical guidelines is critical for deflating the current Mg2+ bubble witnessed in many ribosome and other RNA structures. Herewith, we would like to draw the attention of the researchers interested in the ionic structure of biomolecular systems on the importance and complementarity of stereochemistry and other ion identification techniques such as those pertaining to the detection of anomalous signals of transition metals and K+ We also stress that for the identification of lighter ions such as Mg2+, Na+, , stereochemistry coupled with high resolution structures remain the best currently available option.
Published: 2020

26. Strategic Outlook toward 2030: Japan's research for allergy and immunology – Secondary publication

Author: Masayuki Amagai, Nobuyuki Hizawa, Mitsuhiro Okano, Mayumi Tamari, Hideaki Morita, Takeya Adachi, Komei Ito, Motohiro Ebisawa, Koichiro Asano, Shigeharu Fujieda, Hidehisa Saeki, Akemi Yoshimoto, Kenji Kabashima, Mariko Sonobe, Hiroyuki Arai, Kenji Kondo, Atsuki Fukushima, Eiichi Uchio, Mizuho Nagao, Satoshi Konno, Kazuhiko Yamamoto, Ken Ishii, Keigo Kainuma, Kenji Matsumoto, Japan Agency for Medical Research and Development (AMED), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Tokai University, Keio University School of Medicine [Tokyo, Japan], International University of Health and Welfare (IUHW), Graduate School of Medicine and Faculty of Medicine Kyoto University, Nippon Medical School [Tokyo, Japon], Université de Tsukuba = University of Tsukuba, Kochi University, RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), and The Jikei University School of Medicine
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Biomedical Research, Allergy, Process (engineering), media_common.quotation_subject, [SDV]Life Sciences [q-bio], Immunology, Strategy, Basic law, 03 medical and health sciences, 0302 clinical medicine, Japan, Political science, Allergy and Immunology, Realm, Health care, Hypersensitivity, Immunology and Allergy, Humans, MHLW, Digitization, media_common, Strategic planning, business.industry, General Medicine, 3. Good health, Identification (information), 030104 developmental biology, 030228 respiratory system, business, lcsh:RC581-607, Welfare
Abstract: Strategic Outlook toward 2030: Japan's Research for Allergy and Immunology (Strategy 2030) is the national research strategy based on Japan's Basic Law on Measures Against Allergic Diseases, a first of its kind worldwide. This strategy was established by a multi-disciplinary committee consisting of administrators of the Ministry of Health, Labour and Welfare of Japan, young and senior experts from various research societies and associations, and representatives of patient and public groups. Whereas the issues of transition, integration, and international collaboration have yet to be solved in this research realm in Japan, identification of unmet needs, digitization of information and transparent procedures, and strategic planning for complex problems (a process dubbed MIERUKA by the Toyota Way) are crucial to share and tackle the same vision and goals. The committee developed three specific actions focusing on preemptive treatment, interdisciplinarity and internationality, and life stage. The real success of Strategy 2030 is made by the spontaneous contributions of doctors, dentists, veterinarians, and other medical professionals; basic and clinical research scientists, research supporters, and pharmaceutical/medical device companies; manufacturers of food, healthcare, and home appliances; and patients, their families, and the public. The hope is to establish a stable society in which people can live long, healthy lives, as free as possible from allergic and immunological diseases, at each individual life stage. This article is based on a Japanese review first reported in Arerugi, introduces the developmental process and details of Strategy 2030.
Published: 2020

27. Auto-immunité et médecine personnalisée

Author: Thierry Martin, Aurélien Guffroy, Vincent Gies, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and CCSD, Accord Elsevier
Subjects: 030203 arthritis & rheumatology, 0303 health sciences, medicine.medical_specialty, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Gastroenterology, Precision medicine, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, medicine, Medical physics, Personalized medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology
Published: 2020

28. Le microenvironnement sinusoïdal contrôle la mise en place et la différenciation des macrophages ganglionnaires

Author: Vincent Flacher, Christopher G. Mueller, Abdouramane Camara, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Queen's cancer reserach institute, Immunologie et chimie thérapeutiques (ICT), and Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cell physiology, 0303 health sciences, business.industry, [SDV]Life Sciences [q-bio], Cellular differentiation, Niche, General Medicine, Biology, General Biochemistry, Genetics and Molecular Biology, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Text mining, Immunity, medicine, business, Lymph node, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030215 immunology
Abstract: International audience; No abstract available
Published: 2020

29. Unusual tertiary pairs in eukaryotic tRNAAla

Author: Xiaoling Tong, Fangyin Dai, Xin Ding, Shubo Liang, Eric Westhof, Lu Zheng, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, RNA Folding, Insecta, Base pair, [SDV]Life Sciences [q-bio], RNA, Transfer, Ala, Aminoacylation, Biology, 03 medical and health sciences, Phylogenetics, Transcription (biology), Databases, Genetic, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Letter to the Editor, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Conserved Sequence, Phylogeny, 030304 developmental biology, Mammals, Genetics, Alanine, chemistry.chemical_classification, 0303 health sciences, Base Sequence, 030302 biochemistry & molecular biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ribosomal RNA, Amino acid, chemistry, Transfer RNA, Nucleic Acid Conformation
Abstract: tRNA molecules have well-defined sequence conservations that reflect the conserved tertiary pairs maintaining their architecture and functions during the translation processes. An analysis of aligned tRNA sequences present in the GtRNAdb database (the Lowe Laboratory, University of California, Santa Cruz) led to surprising conservations on some cytosolic tRNAs specific for alanine compared to other tRNA species, including tRNAs specific for glycine. First, besides the well-known G3oU70 base pair in the amino acid stem, there is the frequent occurrence of a second wobble pair at G30oU40, a pair generally observed as a Watson–Crick pair throughout phylogeny. Second, the tertiary pair R15/Y48 occurs as a purine–purine R15/A48 pair. Finally, the conserved T54/A58 pair maintaining the fold of the T-loop is observed as a purine–purine A54/A58 pair. The R15/A48 and A54/A58 pairs always occur together. The G30oU40 pair occurs alone or together with these other two pairs. The pairing variations are observed to a variable extent depending on phylogeny. Among eukaryotes, insects display all variations simultaneously, whereas mammals present either the G30oU40 pair or both R15/A48 and A54/A58. tRNAs with the anticodon 34A(I)GC36 are the most prone to display all those pair variations in mammals and insects. tRNAs with anticodon Y34GC36 have preferentially G30oU40 only. These unusual pairs are not observed in bacterial, nor archaeal, tRNAs, probably because of the avoidance of A34-containing anticodons in four-codon boxes. Among eukaryotes, these unusual pairing features were not observed in fungi and nematodes. These unusual structural features may affect, besides aminoacylation, transcription rates (e.g., 54/58) or ribosomal translocation (30/40).
Published: 2020

30. Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome†

Author: Dominique Burnouf, Florian Veillard, Anne-Marie Lobstein, Clément Monsarrat, Jean-Marc Reichhart, Camille Noûs, Guillaume Compain, Philippe Wolff, Gilles Guichard, Christophe André, Jérôme Wagner, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Modèles Insectes de l'Immunité Innée (M3I), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Cogitamus, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), and Wagner, Jerome
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, DNA polymerase, Peptide, medicine.disease_cause, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Ribosome, 03 medical and health sciences, medicine, Molecular Biology, Escherichia coli, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, DNA clamp, biology, 030306 microbiology, Sciences du Vivant [q-bio]/Biotechnologies, Processivity, biology.organism_classification, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, Chemistry, chemistry, Chemistry (miscellaneous), biology.protein, Antibacterial activity, Bacteria
Abstract: The bacterial processivity factor, or sliding clamp (SC), is a target of choice for new antibacterial drugs development. We have previously developed peptides that target Escherichia coli SC and block its interaction with DNA polymerases in vitro. Here, one such SC binding peptide was fused to a Proline-rich AntiMicrobial Peptide (PrAMP) to allow its internalization into E. coli cells. Co-immunoprecipitation assays with a N-terminally modified bifunctional peptide that still enters the bacteria but fails to interact with the bacterial ribosome, the major target of PrAMPs, demonstrate that it actually interacts with the bacterial SC. Moreover, when compared to SC non-binding controls, this peptide induces a ten-fold higher antibacterial activity against E. coli, showing that the observed antimicrobial activity is linked to SC binding. Finally, an unmodified bifunctional compound significantly increases the survival of Drosophila melanogaster flies challenged by an E. coli infection. Our study demonstrates the potential of PrAMPs to transport antibiotics into the bacterial cytoplasm and validates the development of drugs targeting the bacterial processivity factor of Gram-negative bacteria as a promising new class of antibiotics., Bifunctional peptides targeting both the translation and the replication machineries have been developed and shown to act as new antimicrobials.
Published: 2020

31. Specificities of the plant mitochondrial translation apparatus

Author: Florent Waltz, Philippe Giegé, Nicolas Corre, Yaser Hashem, Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: 0301 basic medicine, Mitochondrial translation, Biology, 7. Clean energy, Ribosome, Mitochondrial Proteins, Mitochondrial Ribosomes, 03 medical and health sciences, 0302 clinical medicine, Eukaryotic translation, Mitochondrial ribosome, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Plant Proteins, 2. Zero hunger, Translation (biology), Cell Biology, Plants, Ribosomal RNA, biology.organism_classification, Mitochondria, Cell biology, 030104 developmental biology, Gene Expression Regulation, Protein Biosynthesis, Molecular Medicine, Pentatricopeptide repeat, Eukaryote, 030217 neurology & neurosurgery
Abstract: Mitochondria are endosymbiotic organelles responsible for energy production in most eukaryotic cells. They host a genome and a fully functional gene expression machinery. In plants this machinery involves hundreds of pentatricopeptide repeat (PPR) proteins. Translation, the final step of mitochondrial gene expression is performed by mitochondrial ribosomes (mitoribosomes). The nature of these molecular machines remained elusive for a very long time. Because of their bacterial origin, it was expected that mitoribosomes would closely resemble bacterial ribosomes. However, recent advances in cryo-electron microscopy have revealed the extraordinary diversity of mitoribosome structure and composition. The plant mitoribosome was characterized for Arabidopsis. In plants, in contrast to other species such as mammals and kinetoplastids where rRNA has been largely reduced, the mitoribosome could be described as a protein/RNA-augmented bacterial ribosome. It has an oversized small subunit formed by expanded ribosomal RNAs and additional protein components when compared to bacterial ribosomes. The same holds true for the large subunit. The small subunit is characterized by a new elongated domain on the head. Among its additional proteins, several PPR proteins are core mitoribosome proteins. They mainly act at the structural level to stabilize and maintain the plant-specific ribosomal RNA expansions but could also be involved in translation initiation. Recent advances in plant mitoribosome composition and structure, its specialization for membrane protein synthesis, translation initiation, the regulation and dynamics of mitochondrial translation are reviewed here and put in perspective with the diversity of mitochondrial translation processes in the green lineage and in the wider context of eukaryote evolution.
Published: 2020

32. Rational Chemical Multifunctionalization of Graphene Interface Enhances Targeted Cancer Therapy

Author: Gonzalo Abellán, Eijiro Miyako, Giacomo Reina, Alberto Bianco, Yue Yu, Matteo Andrea Lucherelli, Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: multifunctionalization, Carbon materials, Cancer therapy, Antineoplastic Agents, Nanotechnology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Catalysis, law.invention, Drug Delivery Systems, law, Cell Line, Tumor, Neoplasms, medicine, Humans, cancer, Doxorubicin, diazonium salts, Càncer, Materials, ComputingMilieux_MISCELLANEOUS, graphite, 010405 organic chemistry, Graphene, Chemistry, Cancer, General Medicine, General Chemistry, Photothermal therapy, medicine.disease, 0104 chemical sciences, Drug delivery, Cancer cell, Surface modification, medicine.drug
Abstract: The synthesis of a drug delivery platform based on graphene was achieved through a step‐by‐step strategy of selective amine deprotection and functionalization. The multifunctional graphene platform, functionalized with indocyanine green, folic acid, and doxorubicin showed an enhanced anticancer activity. The remarkable targeting capacity for cancer cells in combination with the synergistic effect of drug release and photothermal properties prove the great advantage of a combined chemo‐ and phototherapy based on graphene against cancer, opening the doors to future therapeutic applications of this type of material.
Published: 2020

33. Association of COVID-19 mortality with serum selenium, zinc and copper : six observational studies across Europe

Author: Kamil Demircan, Thilo Samson Chillon, Tommy Bracken, Ilaria Bulgarelli, Irene Campi, Gijs Du Laing, Samira Fafi-Kremer, Laura Fugazzola, Alejandro Abner Garcia, Raban Heller, David J. Hughes, Louis Ide, Georg Jochen Klingenberg, Pawel Komarnicki, Zbigniew Krasinski, Alain Lescure, Patrick Mallon, Arash Moghaddam, Luca Persani, Mirko Petrovic, Marek Ruchala, Morgane Solis, Linos Vandekerckhove, Lutz Schomburg, univOAK, Archive ouverte, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), University College Dublin [Dublin] (UCD), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Universiteit Gent = Ghent University (UGENT)
Subjects: [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, SARS-CoV-2, Immunology, COVID-19, trace elements, Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire, mortality, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Zinc, Selenium, nutrition, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine and Health Sciences, Humans, Immunology and Allergy, biomarker, trace elements, SARS-CoV-2, mortality, biomarker, nutrition, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Copper
Abstract: IntroductionCertain trace elements are essential for life and affect immune system function, and their intake varies by region and population. Alterations in serum Se, Zn and Cu have been associated with COVID-19 mortality risk. We tested the hypothesis that a disease-specific decline occurs and correlates with mortality risk in different countries in Europe.MethodsSerum samples from 551 COVID-19 patients (including 87 non-survivors) who had participated in observational studies in Europe (Belgium, France, Germany, Ireland, Italy, and Poland) were analyzed for trace elements by total reflection X-ray fluorescence. A subset (n=2069) of the European EPIC study served as reference. Analyses were performed blinded to clinical data in one analytical laboratory.ResultsMedian levels of Se and Zn were lower than in EPIC, except for Zn in Italy. Non-survivors consistently had lower Se and Zn concentrations than survivors and displayed an elevated Cu/Zn ratio. Restricted cubic spline regression models revealed an inverse nonlinear association between Se or Zn and death, and a positive association between Cu/Zn ratio and death. With respect to patient age and sex, Se showed the highest predictive value for death (AUC=0.816), compared with Zn (0.782) or Cu (0.769).DiscussionThe data support the potential relevance of a decrease in serum Se and Zn for survival in COVID-19 across Europe. The observational study design cannot account for residual confounding and reverse causation, but supports the need for intervention trials in COVID-19 patients with severe Se and Zn deficiency to test the potential benefit of correcting their deficits for survival and convalescence.
Published: 2022

34. The noncoding RNA CcnA modulates the master cell cycle regulators CtrA and GcrA in Caulobacter crescentus

Author: Wanassa Beroual, Karine Prévost, David Lalaouna, Nadia Ben Zaina, Odile Valette, Yann Denis, Meriem Djendli, Gaël Brasseur, Matteo Brilli, Marta Robledo Garrido, Jose-Ignacio Jimenez-Zurdo, Eric Massé, Emanuele G. Biondi, Agence Nationale de la Recherche (France), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie de la Méditerranée (IMM), Université de Sherbrooke (UdeS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Estación Experimental del Zaidín (EEZ), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), and ANR-17-CE20-0011,SymbiontCellCyc,Rôle du cycle cellulaire bactérien dans la fixation symbiotique d'azote chez les Légumineuses(2017)
Subjects: RNA, Untranslated, General Immunology and Microbiology, General Neuroscience, Cell Cycle, Gene Expression Regulation, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, DNA-Binding Proteins, Bacterial Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Caulobacter crescentus, Promoter Regions, Genetic, General Agricultural and Biological Sciences, Transcription Factors
Abstract: Bacteria: are powerful models for understanding how cells divide : and accomplish global regulatory programs. In Caulobacter crescentus, a cascade of essential master regulators supervises the correct and sequential activation of DNA replication, cell division, and development of different cell types. Among them, the response regulator CtrA plays a crucial role coordinating all those functions. Here, for the first time, we describe the role of a novel factor named CcnA (cell cycle noncoding RNA A), a cell cycle–regulated noncoding RNA (ncRNA) located at the origin of replication, presumably activated by CtrA, and responsible for the accumulation of CtrA itself. In addition, CcnA may be also involved in the inhibition of translation of the S-phase regulator, GcrA, by interacting with its 5 untranslated region (5 UTR). Performing in vitro experiments and mutagenesis, we propose a mechanism of action of CcnA based on liberation (ctrA) or sequestration (gcrA) of their ribosome-binding site (RBS). Finally, its role may be conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a potentially conserved process modulating cell cycle in Caulobacterales and Rhizobiales., This research was funded by the Agence Nationale Recherche (ANR; ANR-17-CE20-0011-01) to EGB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Published: 2022

35. CARD9 in neutrophils protects from colitis and controls mitochondrial metabolism and cell survival

Author: Camille Danne, Chloé Michaudel, Jurate Skerniskyte, Julien Planchais, Aurélie Magniez, Allison Agus, Marie-Laure Michel, Bruno Lamas, Gregory Da-Costa, Madeleine Spatz, Cyriane Oeuvray, Chloé Galbert, Maxime Poirier, Yazhou Wang, Alexia Lapiere, Nathalie Rolhion, Tatiana Ledent, Cédric Pionneau, Solenne Chardonnet, Floriant Bellvert, Edern Cahoreau, Amandine Rocher, Rafael Jose Argüello, Carole Peyssonnaux, Sabine Louis, Mathias L. Richard, Philippe Langella, Jamel El-Benna, Benoit Marteyn, Harry Sokol, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris Center for Microbiome Medicine (FHU PaCeMM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Plateforme Post-génomique de la Pitié-Salpêtrière (PASS-P3S), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge (Labex Gr-Ex), Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Funding was provided by the ANR-17-CE15-0019-01 grant and a Marie Skłodowska-Curie Actions fellowship., ANR-17-CE15-0019,MARYLAND,Modulation par Card9 du microbiote intestinal et de sa production d'agonistes Aryl hydrocarbon receptor: mécanisme, potentiel thérapeutique et comme biomarqueur dans les maladies inflammatoires chroniques de l'intestin(2017), LAMAS, Bruno, Modulation par Card9 du microbiote intestinal et de sa production d'agonistes Aryl hydrocarbon receptor: mécanisme, potentiel thérapeutique et comme biomarqueur dans les maladies inflammatoires chroniques de l'intestin - - MARYLAND2017 - ANR-17-CE15-0019 - AAPG2017 - VALID, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MetaToul-MetaboHUB, Institut Cochin, INSERM, CNRS, Université de Paris, Laboratoire d'excellence GR-Ex, Institut Cochin, INSERM, CNRS, UNiversité de Paris, Laboratoire d'excellence GR-Ex, Institut Pasteur, Université de Paris, Inserm 1225 Unité de Pathogenèse des infections Vasculaires, Métabolomique et Fluxomique (MetaToul) (TBI-MetaToul), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Faculte de Medecine Xavier Bichat, Université Paris Diderot - Paris 7 (UPD7), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, IBD, Gastroenterology, Apoptosis, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, mitochondrial activity, Gastrointestinal immune response, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, neutrophils, [SDV.TOX.TCA] Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.TOX]Life Sciences [q-bio]/Toxicology, IBD-Genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology, gut inflammation, CARD9, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: ObjectivesInflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown.DesignWe used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real time bioenergetic profile analysis (Seahorse).ResultsLymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+ cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment. The decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation.ConclusionThese results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.Summary boxWhat is already known about this subject?Inflammatory bowel disease (IBD) results from genetic predisposition, microbiota dysbiosis and environmental factors, but the alterations of the immune response leading to chronic intestinal inflammation are still not fully understood.Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection.However, the cell types and cellular mechanisms involved in the CARD9 protective role against inflammation remain unknown.What are the new findings?CARD9 expression in neutrophils, but not in lymphocytes, epithelial cells or CD11c+ cells, protects against DSS-induced colitis.In the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment.The decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation.How might it impact on clinical practice in the foreseeable future?These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation.Understanding the role of neutrophils in chronic inflammation could lead to innovative therapeutic strategies targeting these key immune cells for various complex diseases.
Published: 2022

36. Discovery of two distinct aminoacyl-tRNA synthetase complexes anchored to the Plasmodium surface tRNA import protein

Author: José R. Jaramillo Ponce, Delphine Kapps, Caroline Paulus, Johana Chicher, Magali Frugier, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), and univOAK, Archive ouverte
Subjects: multiaminoacyl-tRNA synthetase complex, Plasmodium berghei, RNA-binding protein, Protozoan Proteins, Methionine-tRNA Ligase, Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire, Biochemistry, aminoacyl-tRNA synthetase–interacting multifunctional proteins (AIMP), Amino Acyl-tRNA Synthetases, RNA, Transfer, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, aminoacyl-tRNA synthetase, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, tRNA, protein complex, Membrane Proteins, Nuclear Proteins, RNA-Binding Proteins, cell surface protein, Cell Biology, GST-like domain, Neoplasm Proteins, Cytokines, human activities
Abstract: Aminoacyl-tRNA synthetases (aaRSs) attach amino acids to their cognate transfer RNAs. In eukaryotes, a subset of cytosolic aaRSs is organized into a multisynthetase complex (MSC), along with specialized scaffolding proteins referred to as aaRS-interacting multifunctional proteins (AIMPs). In Plasmodium, the causative agent of malaria, the tRNA import protein (tRip), is a membrane protein that participates in tRNA trafficking; we show that tRip also functions as an AIMP. We identified three aaRSs, the glutamyl-tRNA synthetase (ERS), glutaminyl-tRNA synthetase (QRS), and methionyl-tRNA synthetase (MRS), which were specifically coimmunoprecipitated with tRip in Plasmodium berghei blood stage parasites. All four proteins contain an N-terminal glutathione-S-transferase (GST)-like domain that was demonstrated to be involved in MSC assembly. In contrast to previous studies, further dissection of GST-like interactions identified two exclusive heterotrimeric complexes: the Q-complex (tRip-ERS-QRS) and the M-complex (tRip-ERS-MRS). Gel filtration and light scattering suggest a 2:2:2 stoichiometry for both complexes but with distinct biophysical properties and mutational analysis further revealed that the GST-like domains of QRS and MRS use different strategies to bind ERS. Taken together, our results demonstrate that neither the singular homodimerization of tRip nor its localization in the parasite plasma membrane prevents the formation of MSCs in Plasmodium. Besides, the extracellular localization of the tRNA-binding module of tRip is compensated by the presence of additional tRNA-binding modules fused to MRS and QRS, providing each MSC with two spatially distinct functions: aminoacylation of intraparasitic tRNAs and binding of extracellular tRNAs. This unique host-pathogen interaction is discussed.
Published: 2021

37. A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor

Author: Jean-Christophe Paillart, Benjamin Stupfler, Orian Gilmer, Romina Cabrera-Rodríguez, Tanja Seissler, Camille Libre, Julien Batisse, Santiago Guerrero, Roland Marquet, Agustín Valenzuela-Fernández, Andrea Cimarelli, Cédric Verriez, Lucie Etienne, Melanie M. Weber, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Universidad de La Laguna [Tenerife - SP] (ULL), University of Würzburg = Universität Würzburg, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Untranslated region, QH301-705.5, viruses, mRNA, Population, Medicine (miscellaneous), translation, Biology, Protein degradation, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Stress granule, Transcription (biology), [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:610, Biology (General), education, APOBEC3G, 030304 developmental biology, Messenger RNA, education.field_of_study, 0303 health sciences, 030302 biochemistry & molecular biology, virus diseases, Translation (biology), biochemical phenomena, metabolism, and nutrition, HIV-1, Vif, uORF, Cell biology, 3. Good health, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Abstract: The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcription, translation and protein degradation) that together reduce the levels of A3G in cells and prevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5’ untranslated region (5’UTR) of A3G mRNA for this process. A3G translation occurs through a combination of leaky-scanning and translation re-initiation and the presence of an intact uORF decreases the extent of global A3G translation under normal conditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific feature to repress its translation.
Published: 2021

38. Stabilization of Ribosomal RNA of the Small Subunit by Spermidine in Staphylococcus aureus

Author: Margarita Belinite, Iskander Khusainov, Heddy Soufari, Stefano Marzi, Pascale Romby, Marat Yusupov, Yaser Hashem, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Acides Nucléiques : Régulations Naturelle et Artificielle (ARNA), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Kazan Federal University (KFU)
Subjects: RNA Stability, Staphylococcus aureus, QH301-705.5, translation, Translation (biology), Ribosomal RNA, RNA stability, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, Ribosome, Spermidine, chemistry.chemical_compound, Structural biology, chemistry, Protein biosynthesis, Molecular Biosciences, 30S, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biology (General), ribosomal RNA, Molecular Biology, ribosome 70 S, Original Research
Abstract: Cryo-electron microscopy is now used as a method of choice in structural biology for studying protein synthesis, a process mediated by the ribosome machinery. In order to achieve high-resolution structures using this approach, one needs to obtain homogeneous and stable samples, which requires optimization of ribosome purification in a species-dependent manner. This is especially critical for the bacterial small ribosomal subunit that tends to be unstable in the absence of ligands. Here, we report a protocol for purification of stable 30 S from the Gram-positive bacterium Staphylococcus aureus and its cryo-EM structures: in presence of spermidine at a resolution ranging between 3.4 and 3.6 Å and in its absence at 5.3 Å. Using biochemical characterization and cryo-EM, we demonstrate the importance of spermidine for stabilization of the 30 S via preserving favorable conformation of the helix 44.
Published: 2021

39. The HIV-1 Integrase C-Terminal Domain Induces TAR RNA Structural Changes Promoting Tat Binding

Author: Cecilia Rocchi, Camille Louvat, Patrice Gouet, Daniela Lener, Matteo Negroni, Lionel Ballut, Adriana Miele, Francesca Fiorini, Marc Ruff, Christophe Guillon, Julien Batisse, Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioSciences Lyon-Gerland (BLG), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Fiorini, Francesca
Subjects: RNA-protein interaction, [SDV]Life Sciences [q-bio], Response element, Morphogenesis, HIV Integrase, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Tar (tobacco residue), Transcription (biology), [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, TAR RNA, Guide RNA, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, HIV-1 Integrase, Tat, proviral transcription, C-terminal tail, Chemistry, C-terminus, 030302 biochemistry & molecular biology, Organic Chemistry, RNA, General Medicine, 3. Good health, Cell biology, Integrase, Computer Science Applications, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology.protein, RNA, Viral, tat Gene Products, Human Immunodeficiency Virus, RNA, Guide, Kinetoplastida, Transcription Factors
Abstract: International audience; Recent evidence indicates that the HIV-1 Integrase (IN) binds the viral genomic RNA (gRNA), playing a critical role in the morphogenesis of the viral particle and in the stability of the gRNA once in the host cell. By combining biophysical, molecular biology, and biochemical approaches, we found that the 18-residues flexible C-terminal tail of IN acts as a sensor of the peculiar apical structure of the trans-activation response element RNA (TAR), interacting with its hexaloop. We show that the binding of the whole IN C-terminal domain modifies TAR structure, exposing critical nucleotides. These modifications favour the subsequent binding of the HIV transcriptional trans-activator Tat to TAR, finally displacing IN from TAR. Based on these results, we propose that IN assists the binding of Tat to TAR RNA. This working model provides a mechanistic sketch accounting for the emerging role of IN in the early stages of proviral transcription and could help in the design of anti-HIV-1 therapeutics against this new target of the viral infectious cycle.
Published: 2022

40. CCA-addition in the cold: Structural characterization of the psychrophilic CCA-adding enzyme from the permafrost bacterium Planococcus halocryophilus

Author: de Wijn, Raphaël, Rollet, Kévin, Ernst, Felix G.M., Wellner, Karolin, Betat, Heike, Mörl, Mario, Sauter, Claude, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cold adaptation, [SDV]Life Sciences [q-bio], CCA-adding enzyme, Psychrophilic protein, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, SAXS, tRNA, TP248.13-248.65, X-ray crystallography, Biotechnology
Abstract: International audience; CCA-adding enzymes are highly specific RNA polymerases that add and maintain the sequence CC A at tRNA 3'-ends. Recently, we could reveal that cold adaptation of such a polymerase is not only achieved at the expense of enzyme stability, but also at the cost of polymerization fidelity. Enzymes from psychrophilic organisms usually show an increased structural flexibility to enable catalysis at low temperatures. Here, polymerases face a dilemma, as there is a discrepancy between the need for a tightly controlled flexibility during polymerization and an increased flexibility as strategy for cold adaptation. Based on structural and biochemical analyses, we contribute to clarify the cold adaptation strategy of the psychrophilic CCA-adding enzyme from Planococcus halocryophilus, a gram-positive bacterium thriving in the arctic permafrost at low temperatures down to À15°C. A comparison with the closely related enzyme from the thermophilic bacterium Geobacillus stearothermophilus reveals several features of cold adaptation-a significantly reduced amount of alpha-helical elements in the C-terminal tRNA-binding region and a structural adaptation in one of the highly conserved catalytic core motifs located in the N-terminal catalytic core of the enzyme.
Published: 2021

41. The HIV-1 Nucleocapsid Regulates Its Own Condensation by Phase-Separated Activity-Enhancing Sequestration of the Viral Protease during Maturation

Author: Xiao Tan, Robert J. Gorelick, Tuixent Escribà, Gilles Mirambeau, Carine Tisné, Mohamed Ouizougun-Oubari, Jean-Christophe Paillart, Sara Nieto-Marquez, Sébastien Lyonnais, Roland Marquet, Cristina Lorca-Oró, Michèle Reboud-Ravaux, S. Kashif Sadiq, Natalia Gabrielli, Andreas Meyerhans, José M. Gatell, Laure Dufau, Josephine Okoronkwo, Centre d’études des Maladies Infectieuses et Pharmacologie Anti-Infectieuse - [Montpellier] (CEMIPAI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Universitat Pompeu Fabra [Barcelona] (UPF), Heidelberg Institute for Theoretical Studies (HITS ), European Molecular Biology Laboratory (EMBL), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institució Catalana de Recerca i Estudis Avançats (ICREA), Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Biologie intégrative des organismes marins (BIOM), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and HAL-SU, Gestionnaire
Subjects: liquid–liquid phase separation, medicine.medical_treatment, viruses, nucleocapsid, HIV Infections, Microbiology, enzyme catalysis, Article, 03 medical and health sciences, Virology, medicine, Virus maturation, Humans, biomolecular condensates, Guide RNA, atomic-force microscopy, 030304 developmental biology, Ribonucleoprotein, 0303 health sciences, Budding, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Protease, Chemistry, Viral Proteases, Virus Assembly, 030302 biochemistry & molecular biology, RNA, protease, liquid-liquid phase separation, Nucleocapsid Proteins, QR1-502, Reverse transcriptase, molecular dynamics, 3. Good health, Cell biology, Infectious Diseases, Capsid, HIV-1, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: A growing number of studies indicate that mRNAs and long ncRNAs can affect protein populations by assembling dynamic ribonucleoprotein (RNP) granules. These phase-separated molecular 'sponges', stabilized by quinary (transient and weak) interactions, control proteins involved in numerous biological functions. Retroviruses such as HIV-1 form by self-assembly when their genomic RNA (gRNA) traps Gag and GagPol polyprotein precursors. Infectivity requires extracellular budding of the particle followed by maturation, an ordered processing of ∼2400 Gag and ∼120 GagPol by the viral protease (PR). This leads to a condensed gRNA-NCp7 nucleocapsid and a CAp24-self-assembled capsid surrounding the RNP. The choreography by which all of these components dynamically interact during virus maturation is one of the missing milestones to fully depict the HIV life cycle. Here, we describe how HIV-1 has evolved a dynamic RNP granule with successive weak-strong-moderate quinary NC-gRNA networks during the sequential processing of the GagNC domain. We also reveal two palindromic RNA-binding triads on NC, KxxFxxQ and QxxFxxK, that provide quinary NC-gRNA interactions. Consequently, the nucleocapsid complex appears properly aggregated for capsid reassembly and reverse transcription, mandatory processes for viral infectivity. We show that PR is sequestered within this RNP and drives its maturation/condensation within minutes, this process being most effective at the end of budding. We anticipate such findings will stimulate further investigations of quinary interactions and emergent mechanisms in crowded environments throughout the wide and growing array of RNP granules. This work was supported in part by the European Project THINPAD “Targeting the HIV-1 Nucleocapsid Protein to fight Antiretroviral Drug Resistance” (FP7-Grant Agreement 601969), by Foundation Clinic, by ANRS, by SIDACTION, and with federal funds from the NCI/NIH, under Contract No. HHSN261200800001E with Leidos Biomedical Research, Inc. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government (R.J.G.). S.L. acknowledges funding by the Marie-Curie IEF fellowship (FP7-Grant Agreement 237738) and is grateful to Maria Solà (IBMB-CSIC). S.K.S. and A.M. acknowledge support from amfAR Mathilde Krim Fellowship in Basic Biomedical Research number 108680 and the Spanish Ministry of Economy and Competitiveness and FEDER (Grant no. SAF2013-46077-R). S.K.S. also gratefully acknowledges support from the Volkswagen Foundation “Experiment! Funding Initiative” grant number 93874 and from the Klaus Tschira Stiftung.
Published: 2021

42. A conserved uORF impacts APOBEC3G translation and is essential for translational inhibition by the HIV-1 Vif protein

Author: Libre, Camille, Seissler, Tanja, Guerrero, Santiago, Batisse, Julien, Verriez, Cédric, Stupfler, Benjamin, Gilmer, Orian, Weber, Melanie, Cimarelli, Andrea, Etienne, Lucie, Marquet, Roland, Paillart, Jean-Christophe, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and MATHELIN, Sandra
Subjects: [SDV] Life Sciences [q-bio], viruses, [SDV]Life Sciences [q-bio], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, virus diseases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, biochemical phenomena, metabolism, and nutrition, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology
Abstract: The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular cytosine deaminases APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutations during reverse transcription. Vif counteracts A3G by several non-redundant mechanisms (transcription, translation and protein degradation) that concur in reducing the levels of A3G in cell and in preventing its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5′ untranslated region (5′UTR) of A3G mRNA. Extensive mutagenesis of A3G 5′-UTR, combined with an analysis of their translational effect in transfected cells, indicated that the uORF represses A3G translation and that A3G mRNA is translated through a dual leaky-scanning and re-initiation mechanism. Interestingly, the uORF is also mandatory for the Vif-mediated repression of A3G translation. Furthermore, we showed that the redirection of A3G mRNA into stress granules was dependent not only on Vif, but also on the uORF. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific motif to repress its translation.
Published: 2021

43. Quelle taxonomie des maladies inflammatoires en rhumatologie ?: Le concept de psoutte

Author: Messer, Laurent, Felten, Renaud, Duret, Pierre-Marie, Gottenberg, Jacques Eric, Widawski, Laura, Meyer, Alain, Lomo Myazhiom, Aggée Célestin, Spielmann, Lionel, Sibilia, Jean, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Dynamiques européennes (DynamE), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience; La pratique clinique de la médecine nécessite la reconnaissance de la maladie dont souffre le patient par le médecin. Pour cela, celui-ci rationnalise les signes permettant d’isoler une entité réaliste et de la classer dans la nosologie de référence. Contrairement à d’autres pratiques, le modèle biomédical utilise la méthodologie scientifique du recensement, dans une logique de classification pour définir les maladies. Du fait de son processus de simplification, ce modèle néglige les cas de transition ou les cas complexes. En rhumatologie, ce raisonnement classifiant est mis à l’épreuve par le manque d’objectivité et de spécificité des éléments sur lesquels s’appuie le clinicien pour construire le diagnostic, mais aussi par la complexité des mécanismes physiopathologiques des maladies rhumatismales. Ces maladies peuvent en effet se confondre ou s’intriquer, pour aboutir alors à la description de nouvelles entités non envisagées dans les classifications. Nous présentons dans cette revue les difficultés rencontrées au cours de l’exercice de la médecine dans ces contextes, et comment, à partir d’un cas concret, vécu, celles-ci peuvent donner naissance à la proposition d’un nouveau taxon1.
Published: 2021

44. A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Author: Crouchet, Emilie, Bandiera, Simonetta, Fujiwara, Naoto, Li, Shen, El Saghire, Hussein, Fernández-Vaquero, Mirian, Riedl, Tobias, Sun, Xiaochen, Hirschfield, Hadassa, Jühling, Frank, Zhu, Shijia, Roehlen, Natascha, Ponsolles, Clara, Heydmann, Laura, Saviano, Antonio, Qian, Tongqi, Venkatesh, Anu, Lupberger, Joachim, Verrier, Eloi R., Sojoodi, Mozhdeh, Oudot, Marine A., Duong, François H. T., Masia, Ricard, Wei, Lan, Thumann, Christine, Durand, Sarah C., González-Motos, Victor, Heide, Danijela, Hetzer, Jenny, Nakagawa, Shigeki, Ono, Atsushi, Song, Won-Min, Higashi, Takaaki, Sanchez, Roberto, Kim, Rosa S., Bian, C. Billie, Kiani, Karun, Croonenborghs, Tom, Subramanian, Aravind, Chung, Raymond T., Straub, Beate K., Schuppan, Detlef, Ankavay, Maliki, Cocquerel, Laurence, Schaeffer, Evelyne, Goossens, Nicolas, Koh, Anna P., Mahajan, Milind, Nair, Venugopalan D., Gunasekaran, Ganesh, Schwartz, Myron E., Bardeesy, Nabeel, Shalek, Alex K., Rozenblatt-Rosen, Orit, Regev, Aviv, Felli, Emanuele, Pessaux, Patrick, Tanabe, Kenneth K., Heikenwälder, Mathias, Schuster, Catherine, Pochet, Nathalie, Zeisel, Mirjam B., Fuchs, Bryan C., Hoshida, Yujin, Baumert, Thomas F., Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Texas Southwestern Medical Center [Dallas], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Heidelberg [Heidelberg] = Heidelberg University, Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Hiroshima University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Kumamoto University, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), University Medical Center of the Johannes Gutenberg-University Mainz, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Immunopathologie et chimie thérapeutique (ICT), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Geneva University Hospital (HUG), Massachusetts Institute of Technology (MIT), Harvard University, This work was supported by ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (TheraHCC1.0 and 2.0 IHUARC IHU201301187 and IHUARC2019 to T.F.B.), the European Union (ERC-AdG-2014-671231-HEPCIR to T.F.B. and Y.H., EU H2020-667273-HEPCAR to T.F.B. and M.H., and INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2012 to T.F.B. and M.B.Z), ANRS, Paris (2013/108 and ECTZ103701 to T.F.B), NIH (DK099558 to Y. H., and CA233794 to Y.H. and T. F. B, CA140861 to B.C.F., and CA209940, R21CA209940, and R03AI131066 to N.P. and T.F.B.), Cancer Prevention and Research Institute of Texas (RR180016 to Y.H.), US Department of Defense (W81XWH-16-1-0363 to T.F.B. and Y.H.), the Irma T. Hirschl/Monique Weill-Caulier Trust (Y.H.), and the Foundation of the University of Strasbourg (HEPKIN to T. F. B. and Y. H.) and the Institut Universitaire de France (IUF, T.F.B.). M.H. is supported by an ERC CoG grant (HepatoMetaboPath) and EOS grant and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—Project-ID 272983813—TRR 179, and Project-ID 314905040 SFB TR209. This work has been published under the framework of the LABEX ANR-10-LABX-0028_HEPSYS and Inserm Plan Cancer and benefits from funding from the state managed by the French National Research Agency as part of the Investments for the future program., ANR-10-LABX-0028,HepSys,Functional genomics of viral hepatitis and liver disease(2010), European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), European Project: 667273,H2020,H2020-PHC-2015-two-stage,HEP-CAR(2016), Cocquerel, Laurence, Functional genomics of viral hepatitis and liver disease - - HepSys2010 - ANR-10-LABX-0028 - LABX - VALID, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Mechanisms underlying hepatocellular carcinoma pathogenesis and impact of co-morbidities. - HEP-CAR - - H20202016-01-01 - 2019-12-31 - 667273 - VALID, Universität Heidelberg [Heidelberg], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Johannes Gutenberg - Universität Mainz (JGU), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Liver Cirrhosis, Male, Carcinoma, Hepatocellular, Hepatocellular carcinoma, Carcinogenesis, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hepacivirus, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Chemoprevention, Models, Biological, Article, Cohort Studies, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Drug Discovery, Cancer genomics, Cyclic AMP, Animals, Humans, Cyclic AMP Response Element-Binding Protein, Immunologic Surveillance, Liver diseases, Nizatidine, Inflammation, Mice, Knockout, Macrophages, Liver Neoplasms, Prognosis, Hepatitis C, Computational biology and bioinformatics, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Mechanisms of disease, HEK293 Cells, Liver, Hepatocytes, Transcriptome, Signal Transduction
Abstract: Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention., Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.
Published: 2021

45. Correction to ‘ Cis regulation within a cluster of viral microRNAs’

Author: Sébastien Pfeffer, Päivi M. Ojala, Endrit Elbasani, Monika Vilimova, Maud Contrant, Ramy Randrianjafy, Aurélie Fender, Philippe Dumas, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and univOAK, Archive ouverte
Subjects: Gene Expression Regulation, Viral, RNA Folding, 0303 health sciences, AcademicSubjects/SCI00010, Computational biology, Oligonucleotides, Antisense, Biology, Cell Line, MicroRNAs, 03 medical and health sciences, HEK293 Cells, 0302 clinical medicine, Herpesvirus 8, Human, microRNA, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Cis regulation, Cluster (physics), Humans, RNA, Viral, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Erratum, RNA Processing, Post-Transcriptional, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: MicroRNAs (miRNAs) are small regulatory RNAs involved in virtually all biological processes. Although many of them are co-expressed from clusters, little is known regarding the impact of this organization on the regulation of their accumulation. In this study, we set to decipher a regulatory mechanism controlling the expression of the ten clustered pre-miRNAs from Kaposi's sarcoma associated herpesvirus (KSHV). We measured in vitro the efficiency of cleavage of each individual pre-miRNA by the Microprocessor and found that pre-miR-K1 and -K3 were the most efficiently cleaved pre-miRNAs. A mutational analysis showed that, in addition to producing mature miRNAs, they are also important for the optimal expression of the whole set of miRNAs. We showed that this feature depends on the presence of a canonical pre-miRNA at this location since we could functionally replace pre-miR-K1 by a heterologous pre-miRNA. Further in vitro processing analysis suggests that the two stem-loops act in cis and that the cluster is cleaved in a sequential manner. Finally, we exploited this characteristic of the cluster to inhibit the expression of the whole set of miRNAs by targeting the pre-miR-K1 with LNA-based antisense oligonucleotides in cells either expressing a synthetic construct or latently infected with KSHV.
Published: 2021

46. Chemical and Enzymatic Probing of Viral RNAs: From Infancy to Maturity and Beyond

Author: Jean-Christophe Paillart, Erwan Quignon, Anne-Caroline Jousset, Valérie Vivet-Boudou, Roland Marquet, Orian Gilmer, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Computer science, capillary electrophoresis, Chemical probe, Review, Computational biology, 010402 general chemistry, 01 natural sciences, Microbiology, Primer extension, DNA sequencing, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Virology, mutational profiling, Humans, structure, Molecular Biology, 030304 developmental biology, 0303 health sciences, Sequence Analysis, RNA, chemical probe, High-Throughput Nucleotide Sequencing, high-throughput sequencing, RNA, QR1-502, 0104 chemical sciences, Infectious Diseases, enzymatic probe, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Nucleic Acid Conformation, RNA, Viral, DECIPHER, SHAPE
Abstract: International audience; RNA molecules are key players in a variety of biological events, and this is particularly true for viral RNAs. To better understand the replication of those pathogens and try to block them, special attention has been paid to the structure of their RNAs. Methods to probe RNA structures have been developed since the 1960s; even if they have evolved over the years, they are still in use today and provide useful information on the folding of RNA molecules, including viral RNAs. The aim of this review is to offer a historical perspective on the structural probing methods used to decipher RNA structures before the development of the selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) methodology and to show how they have influenced the current probing techniques. Actually, these technological breakthroughs, which involved advanced detection methods, were made possible thanks to the development of next-generation sequencing (NGS) but also to the previous works accumulated in the field of structural RNA biology. Finally, we will also discuss how high-throughput SHAPE (hSHAPE) paved the way for the development of sophisticated RNA structural techniques.
Published: 2021

47. Cis regulation within a cluster of viral microRNAs

Author: Aurélie Fender, Maud Contrant, Philippe Dumas, Sébastien Pfeffer, Monika Vilimova, Päivi M. Ojala, Endrit Elbasani, Ramy Randrianjafy, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), ANR-17-EURE-0023,IMCBio,Integrative Molecular and Cellular Biology(2017), ANR-10-LABX-0036,NetRNA,Network of regulatory RNAs across kingdoms and dynamical responses to biotic and abiotic stresses.(2010), European Project: 647455,H2020,ERC-2014-CoG,RegulRNA(2016), University of Helsinki, univOAK, Archive ouverte, CAN-PRO - Translational Cancer Medicine Program, Department of Pathology, Biosciences, and Medicum
Subjects: EXPRESSION, AcademicSubjects/SCI00010, BIOGENESIS, HERPESVIRUS, PROTEIN, Heterologous, Computational biology, Biology, Cleavage (embryo), PATHWAY, 03 medical and health sciences, microRNA, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, RNA and RNA-protein complexes, Cluster (physics), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Synthetic construct, 030304 developmental biology, 0303 health sciences, LATENCY, IDENTIFICATION, Mechanism (biology), 030302 biochemistry & molecular biology, TERTIARY STRUCTURE, In vitro, Cell biology, 3. Good health, Mutational analysis, TARGET, MIRNAS, Antisense oligonucleotides, Cis regulation, 1182 Biochemistry, cell and molecular biology, Cytokinesis
Abstract: MicroRNAs (miRNAs) are small regulatory RNAs involved in virtually all biological processes. Although many of them are co-expressed from clusters, little is known regarding the impact of this organization on the regulation of their accumulation. In this study, we set to decipher a regulatory mechanism controlling the expression of the ten clustered pre-miRNAs from Kaposi’s sarcoma associated herpesvirus (KSHV). We measured in vitro the efficiency of cleavage of each individual pre-miRNA by the Microprocessor and found that pre-miR-K1 and -K3 were the most efficiently cleaved pre-miRNAs. A mutational analysis showed that, in addition to producing mature miRNAs, they are also important for the optimal expression of the whole set of miRNAs. We showed that this feature depends on the presence of a canonical pre-miRNA at this location since we could functionally replace pre-miR-K1 by a heterologous pre-miRNA. Further in vitro processing analysis suggests that the two stem-loops act in cis and that the cluster is cleaved in a sequential manner. Finally, we exploited this characteristic of the cluster to inhibit the expression of the whole set of miRNAs by targeting the pre-miR-K1 with LNA-based antisense oligonucleotides in cells either expressing a synthetic construct or latently infected with KSHV.
Published: 2021

48. Importance of Viral Late Domains in Budding and Release of Enveloped RNA Viruses

Author: Jean-Christophe Paillart, Serena Bernacchi, Lisa Welker, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN
Subjects: ESCRT machinery, viruses, Review, budding, Biology, medicine.disease_cause, Virus Replication, Microbiology, ESCRT, Conserved sequence, viral assembly, 03 medical and health sciences, late assembly domains, Retrovirus, Membrane fission, RNA enveloped viruses, Virology, medicine, Humans, RNA Viruses, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Virus Release, 030304 developmental biology, 0303 health sciences, Budding, Mutation, Endosomal Sorting Complexes Required for Transport, Virus Assembly, 030302 biochemistry & molecular biology, Ubiquitination, Virion, RNA, biology.organism_classification, retroviral gag precursor, QR1-502, 3. Good health, Cell biology, structural viral proteins, retrovirus, Infectious Diseases, Viral replication, Protein Binding
Abstract: Late assembly (L) domains are conserved sequences that are necessary for the late steps of viral replication, acting like cellular adaptors to engage the ESCRT membrane fission machinery that promote virion release. These short sequences, whose mutation or deletion produce the accumulation of immature virions at the plasma membrane, were firstly identified within retroviral Gag precursors, and in a further step, also in structural proteins of many other enveloped RNA viruses including arenaviruses, filoviruses, rhabdoviruses, reoviruses, and paramyxoviruses. Three classes of L domains have been identified thus far (PT/SAP, YPXnL/LXXLF, and PPxY), even if it has recently been suggested that other motifs could act as L domains. Here, we summarize the current state of knowledge of the different types of L domains and their cellular partners in the budding events of RNA viruses, with a particular focus on retroviruses.
Published: 2021

49. Correction: Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome

Author: Christophe André, Florian Veillard, Philippe Wolff, Anne-Marie Lobstein, Guillaume Compain, Clément Monsarrat, Jean-Marc Reichhart, Dominique Y. Burnouf, Gilles Guichard, Jérôme E. Wagner, Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, 010405 organic chemistry, [SDV]Life Sciences [q-bio], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 01 natural sciences, Biochemistry, Genetics and Molecular Biology (miscellaneous), Biochemistry, 0104 chemical sciences, 3. Good health, 03 medical and health sciences, Chemistry, Chemistry (miscellaneous), [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology
Abstract: Correction for ‘Antibacterial activity of a dual peptide targeting the Escherichia coli sliding clamp and the ribosome’ by Christophe André et al., RSC Chem. Biol., 2020, 1, 137–147, DOI: 10.1039/D0CB00060D.
Published: 2021

50. RNA Modifications in Pathogenic Bacteria: Impact on Host Adaptation and Virulence

Author: Victor Loegler, Heemee Devi Bunwaree, Martin Gobry, Laura Antoine, Stefano Marzi, Pascale Romby, Roberto Bahena-Ceron, Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: mRNA, Virulence, host-adaptation, Review, Computational biology, QH426-470, Biology, Host Adaptation, 03 medical and health sciences, RNA modifications, 0302 clinical medicine, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA Processing, Post-Transcriptional, Nucleic acid structure, tRNA, Gene, Genetics (clinical), small non-coding RNA, 030304 developmental biology, 0303 health sciences, Messenger RNA, Bacteria, RNA, pathogenic bacteria, Ribosomal RNA, stress adaptation, RNA, Bacterial, Host-Pathogen Interactions, Transfer RNA, Host adaptation, ribosomal RNA, 030217 neurology & neurosurgery
Abstract: RNA modifications are involved in numerous biological processes and are present in all RNA classes. These modifications can be constitutive or modulated in response to adaptive processes. RNA modifications play multiple functions since they can impact RNA base-pairings, recognition by proteins, decoding, as well as RNA structure and stability. However, their roles in stress, environmental adaptation and during infections caused by pathogenic bacteria have just started to be appreciated. With the development of modern technologies in mass spectrometry and deep sequencing, recent examples of modifications regulating host-pathogen interactions have been demonstrated. They show how RNA modifications can regulate immune responses, antibiotic resistance, expression of virulence genes, and bacterial persistence. Here, we illustrate some of these findings, and highlight the strategies used to characterize RNA modifications, and their potential for new therapeutic applications.
Published: 2021

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