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2. Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity

Author

Giessner, Caroline, Millet, Virginie, Mostert, Konrad J., Gensollen, Thomas, Manh, Thien-Phong Vu, Garibal, Marc, Dieme, Binta, Attaf-Bouabdallah, Noudjoud, Chasson, Lionel, Brouilly, Nicolas, Laprie, Caroline, Lesluyes, Tom, Blay, Jean Yves, Shintu, Laetitia, Martin, Jean Charles, Strauss, Erick, Galland, Franck, Naquet, Philippe, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut Bergonié [Bordeaux], UNICANCER, Equipe 11, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Prémilleux, Annick, Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagerie et cerveau, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, Centre de Recherche en Cancérologie de Lyon (CRCL), 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)-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), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Centre recherche en CardioVasculaire et Nutrition (C2VN), 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)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL)

Subjects
[SDV] Life Sciences [q-bio], Vegetal Biology, [SDV]Life Sciences [q-bio], phosphorylation oxydative, sarcome, activité mitochondriale, cysteamine, glycolyse, Research Articles, Biologie végétale, Research Article
Abstract

Expression of the Vnn1 pantetheinase by sarcomas is tumor suppressive by limiting the use of aerobic glycolysis for growth and rescuing mitochondrial activity through CoA regeneration., Like other tumors, aggressive soft tissue sarcomas (STS) use glycolysis rather than mitochondrial oxidative phosphorylation (OXPHOS) for growth. Given the importance of the cofactor coenzyme A (CoA) in energy metabolism, we investigated the impact of Vnn1 pantetheinase—an enzyme that degrades pantetheine into pantothenate (vitamin B5, the CoA biosynthetic precursor) and cysyteamine—on tumor growth. Using two models, we show that Vnn1+ STS remain differentiated and grow slowly, and that in patients a detectable level of VNN1 expression in STS is associated with an improved prognosis. Increasing pantetheinase activity in aggressive tumors limits their growth. Using combined approaches, we demonstrate that Vnn1 permits restoration of CoA pools, thereby maintaining OXPHOS. The simultaneous production of cysteamine limits glycolysis and release of lactate, resulting in a partial inhibition of STS growth in vitro and in vivo. We propose that the Warburg effect observed in aggressive STS is reversed by induction of Vnn1 pantetheinase and the rewiring of cellular energy metabolism by its products.

Published
2018

4. Draft Genome Sequencing of Methanobrevibacter oralis Strain JMR01, Isolated from the Human Intestinal Microbiota

Author

Aghnatios, Rita, Cayrou, Caroline, Garibal, Marc, Robert, Catherine, Azza, Said, Raoult, Didier, Drancourt, Michel, Khelaifia, Saber, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité des Rickettsies et pathogènes émergents (URPE), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), and INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48

Subjects
2. Zero hunger, Genetics, 0303 health sciences, Strain (chemistry), 030306 microbiology, ved/biology, ved/biology.organism_classification_rank.species, Biology, Oral cavity, C content, Genome, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], DNA sequencing, Microbiology, 03 medical and health sciences, Open reading frame, CRISPR, Prokaryotes, Methanobrevibacter oralis, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Molecular Biology, 030304 developmental biology
Abstract

International audience; Methanobrevibacter oralis, an anaerobic methanogenic archaeon, has been previously isolated from the human oral cavity. Here, sequencing a stool isolate (strain JMR01) yielded a 2.065-Mb genome with a 27.78% GC content containing a total of 2,042 open reading frames and 3 clusters of regularly interspaced short palindromic repeat (CRISPR) loci with associated Cas proteins. Address correspondence to Michel Drancourt, michel.drancourt@univ-amu.fr. M ethanobrevibacter oralis was initially isolated from human subgingival plaque (1), and further studies associated this methanogen with subgingival diseases, including periodontitis (2). We recently demonstrated a significant correlation between the M. oralis charge and the severity of periodontitis (3). Furthermore , M. oralis DNA was detected in the human gut, and we previously reported the first isolation of M. oralis (strain JMR01) from the human gut (4). M. oralis strain JMR01 is a strict anaer-obic archaeon with optimal growth at 37°C (pH 7.5) and 1.5 g/liter NaCl. Methane is produced by reducing acetate or H 2-CO 2 as an electron donor. Rumen fluid and vitamin solutions are required for growth and a volatile fatty acid mixture stimulates growth. Phylogenetic classification based on the 16S rRNA gene sequence (GenBank accession number KC616346) confirmed the affiliation of the M. oralis strain JMR01 herein sequenced with the genus Methanobrevibacter and yielded a sequence similarity of 99% with the reference strain M. oralis DSM 7256 (GenBank accession number HE654003). The M. oralis strain JMR01 complete genome was sequenced by combining shotgun and 3-kb paired-end libraries using high-throughput 454 pyrosequencing (454 Life Sciences-Roche, Boulogne-Billancourt, France). Sequence reads were assembled using a Newbler assembler 2.8 (20120726_1306) (Roche), and 136 contigs were generated into 14 scaffolds. A preliminary open reading frame (ORF) prediction was conducted by automated annotation with Glimmer (http://www .cbcb.umd.edu/software/glimmer/) and RAST (5). The annotation was manually curated using BLAST and the nr database of NCBI. The CRISPR finder (http://crispr.u-psud.fr/Server/) was used to detect and identify CRISPR repeat and spacer sequences in the genome. The M. oralis genome consists of a 2,065,764-bp circular chromosome (with a GC content of 27.78%). A total of 2,042 ORFs were recovered, encoding proteins involved in functions previously assigned in other related Methanobrevibacter organisms (6). Likewise, the M. oralis genome contains three CRISPR loci and associated proteins (Cas), as previously found in Methanobre-vibacter arboriphilicus (7). We previously observed that M. oralis, an inhabitant of the oral cavity, survives in the acidity of the stomach (S. Khelaifia and M. Drancourt, unpublished data), giving it an opportunity to establish itself in the digestive tract. Accordingly, we isolated M. oralis from the human gut. The availability of the M. oralis genome will give the opportunity to develop genotyping methods to investigate the diversity of this frequently detected human archaeon. Moreover, the isolation of a new M. oralis strain from the human gut, as well as its genome sequencing, can increase knowledge of this neglected component of the human gut microbiota. Nucleotide sequence accession numbers. The Methanobre-vibacter oralis strain JMR01 genome sequence has been deposited in EMBL under the accession numbers CBWS010000001 through CBWS010000060. The whole-genome shotgun project has been deposited in GenBank under the accession number CBWS000000000. ACKNOWLEDGMENT

Published
2014

8. Divergent transcription is associated with promoters of transcriptional regulators

Author

Lepoivre, Cyrille, primary, Belhocine, Mohamed, additional, Bergon, Aurélie, additional, Griffon, Aurélien, additional, Yammine, Miriam, additional, Vanhille, Laurent, additional, Zacarias-Cabeza, Joaquin, additional, Garibal, Marc-Antoine, additional, Koch, Frederic, additional, Maqbool, Muhammad Ahmad, additional, Fenouil, Romain, additional, Loriod, Beatrice, additional, Holota, Hélène, additional, Gut, Marta, additional, Gut, Ivo, additional, Imbert, Jean, additional, Andrau, Jean-Christophe, additional, Puthier, Denis, additional, and Spicuglia, Salvatore, additional

Published
2013
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9. Divergent transcription is associated with promoters of transcriptional regulators.

Author

Andrau, Jean-Christophe, Belhocine, Mohamed, Bergon, Aurélie, Fenouil, Romain, Garibal, Marc-Antoine, Griffon, Aurélien, Gut, Marta, Gut, Ivo, Holota, Hélène, Imbert, Jean, Koch, Frederic, Lepoivre, Cyrille, Loriod, Beatrice, Maqbool, Muhammad Ahmad, Puthier, Denis, Spicuglia, Salvatore, Vanhille, Laurent, Yammine, Miriam, and Zacarias-Cabeza, Joaquin

Subjects
NON-coding RNA, DEVELOPMENTAL genetics, RNA polymerases, ANTISENSE RNA, CELL anatomy
Abstract

Divergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are a hallmark of active promoters, while longer transcripts can be detected antisense from active genes in conditions where the RNA degradation machinery is inhibited. Moreover, many described long non-coding RNAs (lncRNAs) are transcribed antisense from coding gene promoters. However, the general significance of divergent lncRNA/mRNA gene pair transcription is still poorly understood. Here, we used strandspecific RNA-seq with high sequencing depth to thoroughly identify antisense transcripts from coding gene promoters in primary mouse tissues. Results We found that a substantial fraction of coding-gene promoters sustain divergent transcription of long non-coding RNA (lncRNA)/mRNA gene pairs. Strikingly, upstream antisense transcription is significantly associated with genes related to transcriptional regulation and development. Their promoters share several characteristics with those of transcriptional developmental genes, including very large CpG islands, high degree of conservation and epigenetic regulation in ES cells. In-depth analysis revealed a unique GC skew profile at these promoter regions, while the associated coding genes were found to have large first exons, two genomic features that might enforce bidirectional transcription. Finally, genes associated with antisense transcription harbor specific H3K79me2 epigenetic marking and RNA polymerase II enrichment profiles linked to an intensified rate of early transcriptional elongation. Conclusions We concluded that promoters of a class of transcription regulators are characterized by a specialized transcriptional control mechanism, which is directly coupled to relaxed bidirectional transcription. [ABSTRACT FROM AUTHOR]

Published
2013
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10. Draft genome of Gemmata massiliana sp. nov, a water-borne Planctomycetes species exhibiting two variants

Author

Aghnatios, Rita, Cayrou, Caroline, Garibal, Marc, Robert, Catherine, Azza, Said, Raoult, Didier, Drancourt, Michel, Azza, Saïd, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Unité des Rickettsies et pathogènes émergents (URPE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48

Subjects
Genetics, Genome, biology, Planctomycetes, Culture, Chromosome, 16S ribosomal RNA, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Short Genome Report, Microbiology, chemistry.chemical_compound, Plasmid, chemistry, Gemmata obscuriglobus, Gemmata massiliana, Hospital water network, Peptidoglycan, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Gene, Gemmata, Bacteria
Abstract

Gemmata massiliana is a new Planctomycetes bacterium isolated from a hospital water network in France, using a new culture medium. It is an aerobic microorganism with optimal growth at pH 8, at 30 °C and salinity ≤ 1.25 % NaCl. G. massiliana is resistant to β-lactam antibiotics, due to lack of peptidoglycan in its cell wall.G. massiliana shares a 97 % 16S rRNA gene sequence similarity with the nearest species, Gemmata obscuriglobus; and 99 % similarity with unnamed soil isolates. Its 9,249,437-bp genome consists in one chromosome and no detectable plasmid and has a 64.07 % G + C content, 32.94 % of genes encoding for hypothetical proteins. The genome contains an incomplete 19.6-kb phage sequence, 26 CRISPRs, 3 CAS and 15 clusters of secondary metabolites. G. massiliana genome increases knowledge of a poorly known world of bacteria. Electronic supplementary material The online version of this article (doi:10.1186/s40793-015-0103-0) contains supplementary material, which is available to authorized users.

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