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Your search keyword '"Christine Göbel"' showing total 2 results
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2 results on '"Christine Göbel"'

1. MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells.

Author

Manuel Albanese, Yen-Fu Adam Chen, Corinna Hüls, Kathrin Gärtner, Takanobu Tagawa, Ernesto Mejias-Perez, Oliver T Keppler, Christine Göbel, Reinhard Zeidler, Mikhail Shein, Anne K Schütz, and Wolfgang Hammerschmidt

Subjects
Genetics, QH426-470
Abstract

Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells' transcriptome. The extent to which miRNAs are exported via the EV route and whether they contribute to cell-cell communication are controversial. To address these issues, we defined multiple properties of EVs and analyzed their capacity to deliver packaged miRNAs into target cells to exert biological functions. We applied well-defined approaches to produce and characterize purified EVs with or without specific viral miRNAs. We found that only a small fraction of EVs carried miRNAs. EVs readily bound to different target cell types, but EVs did not fuse detectably with cellular membranes to deliver their cargo. We engineered EVs to be fusogenic and document their capacity to deliver functional messenger RNAs. Engineered fusogenic EVs, however, did not detectably alter the functionality of cells exposed to miRNA-carrying EVs. These results suggest that EV-borne miRNAs do not act as effectors of cell-to-cell communication.

Published
2021
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2. Structural basis of DNA methylation-dependent site selectivity of the Epstein–Barr virus lytic switch protein ZEBRA/Zta/BZLF1

Author

Florent Bernaudat, Montse Gustems, Johannes Günther, Mizar F Oliva, Alexander Buschle, Christine Göbel, Priscilla Pagniez, Julien Lupo, Luca Signor, Christoph W Müller, Patrice Morand, Michael Sattler, Wolfgang Hammerschmidt, Carlo Petosa, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institute of Structural Biology (Neuherberg), Helmholtz-Zentrum München (HZM), Institut Laue-Langevin (ILL), ILL, Platforms of the Grenoble Instruct-ERIC center (ISBG, UMS 3518 CNRS-CEA-UGA-EMBL), Grenoble Partnership for Structural Biology (PSB), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-09-MIEN-0008,EBV-Lyt,Bases moléculaires et identification d'inhibiteurs de l'activation du cycle lytique du virus d'Epstein-Barr(2009), and Helmholtz Zentrum München = German Research Center for Environmental Health

Subjects
Gene Expression Regulation, Viral, 0303 health sciences, Epstein-Barr Virus Infections, Herpesvirus 4, Human, animal structures, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], genetic structures, AcademicSubjects/SCI00010, 030302 biochemistry & molecular biology, DNA Methylation, Virus Replication, 03 medical and health sciences, Viral Proteins, HEK293 Cells, nervous system, Structural Biology, DNA, Viral, Genetics, behavior and behavior mechanisms, Trans-Activators, Humans, psychological phenomena and processes, 030304 developmental biology, Protein Binding
Abstract

In infected cells, Epstein–Barr virus (EBV) alternates between latency and lytic replication. The viral bZIP transcription factor ZEBRA (Zta, BZLF1) regulates this cycle by binding to two classes of ZEBRA response elements (ZREs): CpG-free motifs resembling the consensus AP-1 site recognized by cellular bZIP proteins and CpG-containing motifs that are selectively bound by ZEBRA upon cytosine methylation. We report structural and mutational analysis of ZEBRA bound to a CpG-methylated ZRE (meZRE) from a viral lytic promoter. ZEBRA recognizes the CpG methylation marks through a ZEBRA-specific serine and a methylcytosine-arginine-guanine triad resembling that found in canonical methyl-CpG binding proteins. ZEBRA preferentially binds the meZRE over the AP-1 site but mutating the ZEBRA-specific serine to alanine inverts this selectivity and abrogates viral replication. Our findings elucidate a DNA methylation-dependent switch in ZEBRA’s transactivation function that enables ZEBRA to bind AP-1 sites and promote viral latency early during infection and subsequently, under appropriate conditions, to trigger EBV lytic replication by binding meZREs.

Published
2021

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