1. The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication
- Author
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Maud Dupont, Tim Krischuns, Quentin Giai-Gianetto, Sylvain Paisant, Stefano Bonazza, Jean-Baptiste Brault, Thibaut Douché, Joel I Perez-Perri, Matthias W Hentze, Stephen Cusack, Mariette Matondo, Catherine Isel, David G Courtney, Nadia Naffakh, Biologie des ARN et virus influenza - RNA Biology of Influenza Virus (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme de Protéomique / Proteomics platform, Université Paris Cité (UPCité)-Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Wellcome-Wolfson Institute for Experimental Medicine, Queen's University [Belfast] (QUB), European Molecular Biology Laboratory [Heidelberg] (EMBL), European Molecular Biology Laboratory [Grenoble] (EMBL), This work was funded by the Agence Nationale de la Recherche [ANR-18-CE18-0028 to SC and NN, ANR-10-LABX-62IBEID to MM and NN, ANR-21-CE35-0007 to MM], the Marie-Skłodowska Curie Global Fellowship [MSCA-IF-GF:747810 to DGC], and the European Research Council Fellowship [PTFLU 949506 to DGC and SB]. Funding for open access charges [Agence Nationale de la Recherche/ANR-10-LABX-62IBEID], We would like to thank Dr. Feng Zhang (Broad Institute, Cambridge, USA), Dr. Mikhael Matrosovich (Philipps Universität, Marburg, Germany), Dr. Pierre-Olivier Vidalain (CIRI, Lyon), Dr. Daniel Marc (INRAE, Nouzilly, France), Dr. Caroline Demeret, Dr. Sandie Munier and the National Reference Center for Respiratory Viruses (all at Institut Pasteur, Paris, France) and for sharing reagents used in this work. We would like to thank Yves Jacob, Anastasia Komarova and Valérie Najburg (Institut Pasteur, Paris, France) for helpful discussions. Some figures were created with BioRender.com, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and ANR-21-CE35-0007,PureMagRupture,Un flux de travail de la gMEP (Genetic magnetic-extraction-proteomics) pour comprendre le lien entre la rupture vacuolaire de Shigella et l'autophagie(2021)
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[SDV]Life Sciences [q-bio] - Abstract
Recent technical advances have significantly improved our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells, with a particular focus on the RBPs that interact with cellular polyadenylated mRNAs. However, recent studies utilising the same technologies have begun to tease apart the RBP interactome of viral mRNAs, notably SARS-CoV-2, revealing both similarities and differences between the RBP profiles of viral and cellular mRNAs. Herein, we comprehensively identified the RBPs that associate with the NP mRNA of an influenza A virus. Moreover, we provide evidence that the viral polymerase is essential for the recruitment of RPBs to viral mRNAs through direct polymerase-RBP interactions during transcription. We show that loss of TDP-43, which associates with the viral mRNAs, results in lower levels of viral mRNAs within infected cells, and a decreased yield of infectious viral particles. Overall, our results uncover an important role for TDP-43 in the influenza A virus replication cycle via a direct interaction with viral mRNAs, and point to a role of the viral polymerase in orchestrating the assembly of viral mRNPs.
- Published
- 2023