Identifying cellular RNA-binding proteins during infection uncovers a role for MKRN2 in influenza mRNA trafficking

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.