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

Archive ouverte

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

Edité par CCSD ; Oxford University Press -

International audience. 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.

Suggestions

Du même auteur

The host RNA polymerase II C-terminal domain is the anchor for replication of the influenza virus genome

Archive ouverte | Krischuns, Tim | CCSD

International audience. Abstract The current model is that the influenza virus polymerase (FluPol) binds either to host RNA polymerase II (RNAP II) or to the acidic nuclear phosphoprotein 32 (ANP32), which drives it...

Type B and type A influenza polymerases have evolved distinct binding interfaces to recruit the RNA polymerase II CTD

Archive ouverte | Krischuns, Tim | CCSD

International audience. During annual influenza epidemics, influenza B viruses (IBVs) co-circulate with influenza A viruses (IAVs), can become predominant and cause severe morbidity and mortality. Phylogenetic analy...

Mechanism of Co-Transcriptional Cap-Snatching by Influenza Polymerase

Archive ouverte | Rotsch, Alexander Helmut | CCSD

Abstract Influenza virus mRNA is stable and competent for nuclear export and translation because it receives a 5′ cap(1) structure in a process called cap-snatching 1 . During cap-snatching, the viral RNA-dependent RNA polymerase ...

Chargement des enrichissements...