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Utilisation of RNA-binding proteins (RBPs) is an important aspect of post-transcriptional regulation of viral RNA. Viruses such as influenza A viruses (IAV) interact with RBPs to regulate processes including splicing, nuclear export and trafficking, while also encoding RBPs within their genomes, such as NP and NS1. But with almost 1000 RBPs encoded within the human genome it is still unclear what role, if any, many of these proteins play during viral replication. Using the RNA interactome capture (RIC) technique, we isolated RBPs from IAV infected cells to unravel the RBPome of mRNAs from IAV infected human cells. This led to the identification of one particular RBP, MKRN2, that associates with and positively regulates IAV mRNA. Through further validation, we determined that MKRN2 is involved in the nuclear-cytoplasmic trafficking of IAV mRNA potentially through an association with the RNA export mediator GLE1. In the absence of MKRN2, IAV mRNAs accumulate in the nucleus of infected cells, which may lead to their degradation by the nuclear RNA exosome complex. MKRN2, therefore, appears to be required for the efficient nuclear export of IAV mRNAs in human cells. Author summary: During the course of an influenza A virus infection various cellular proteins and systems must be hijacked for the virus to successfully replicate and spread to neighbouring cells. This includes cellular translation machinery, splicing components, and systems for RNA trafficking. Herein, we sought to uncover a subset of RNA-binding proteins utilised by IAV mRNA in the hopes that, by revealing an essential part in the viral life cycle future therapeutics could be targeted to prevent this step happening and thus block virus spread. Through our methods of molecular virology and mass spectrometry we uncovered the cellular protein MKRN2, previously not implicated in any stages of the viral life cycle. We found that MKRN2 binds to IAV mRNAs and is involved in the trafficking of these viral mRNAs out of the nucleus and into the cytoplasm, where they can then be translated into viral proteins. By blocking MKRN2 we could significantly inhibit normal viral replication. We speculate that by preventing these viral mRNAs from being efficiently trafficked out of the nucleus, they are more likely to be degraded by RNA exonucleases found within the nucleus. [ABSTRACT FROM AUTHOR]