The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication

Maud Dupont, Tim Krischuns, Quentin Giai Gianetto, Sylvain Paisant, Stefano Bonazza, Jean-Baptiste Brault, Thibaut Douché, Benoît Arragain, Alberto Florez-Prada, Joel I Perez-Perri, Matthias W Hentze, Stephen Cusack, Mariette Matondo, Catherine Isel, David G Courtney, Nadia Naffakh

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Abstract

Genome-wide approaches have significantly advanced our knowledge of the repertoire of RNA-binding proteins (RBPs) that associate with cellular polyadenylated mRNAs within eukaryotic cells. Recent studies focusing on the RBP interactomes of viral mRNAs, notably SARS-Cov-2, have revealed both similarities and differences between the RBP profiles of viral and cellular mRNAs. However, the RBPome of influenza virus mRNAs remains unexplored. Herein, we identify RBPs that associate with the viral mRNA encoding the nucleoprotein (NP) of an influenza A virus. Focusing on TDP-43, we show that it binds several influenza mRNAs beyond the NP-mRNA, and that its depletion results in lower levels of viral mRNAs and proteins within infected cells, and a decreased yield of infectious viral particles. We provide evidence that the viral polymerase recruits TDP-43 onto viral mRNAs through a direct interaction with the disordered C-terminal domain of TDP-43. Notably, other RBPs found to be associated with influenza virus mRNAs also interact with the viral polymerase, which points to a role of the polymerase in orchestrating the assembly of viral messenger ribonucleoproteins.
Original languageEnglish
Number of pages23
JournalNucleic Acids Research
Volume13
Early online date30 Apr 2024
DOIs
Publication statusEarly online date - 30 Apr 2024

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