The RBPome of influenza A virus mRNA reveals a role for TDP-43 in viral replication
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ABSTRACT: Recent technical advances have resulted in a significant increase in our understanding of the RNA-binding protein (RBP) repertoire present within eukaryotic cells. A particular focus has been 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, most notably SARS-CoV-2, demonstrating clear similarities but also differences between the RBP profiles of viral and cellular mRNAs. Herein, for the first time we comprehensively mapped 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, that associates with the viral mRNA, results in a decrease in viral mRNA availability within infected cells, with an impact on the accumulation of viral genomic RNA and the yield of infectious viral particles. Overall, we uncover an important role for TDP-43 in the influenza A virus replication cycle via a direct interaction with viral mRNAs and we demonstrate an essential role of the viral polymerase in orchestrating the assembly of viral mRNPs.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (human) Influenza A Virus (a/ws/1933(h1n1))
TISSUE(S): Cell Line Cell
SUBMITTER:
Thibaut Douché
LAB HEAD: Nadia Naffakh
PROVIDER: PXD040783 | Pride | 2024-04-16
REPOSITORIES: Pride
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