The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression

Lea Gaucherand; Brittany K. Porter; Summer K. Schmaling; Christopher Harley Rycroft; Yuzo Kevorkian; Craig McCormick; Denys A. Khaperskyy; Marta Maria Gaglia

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/442996 doi: bioRxiv preprint phenotype between IAV wt and PA(fs) (Jagger et al., 2012) . However, they inserted the stop 406 codon after 16 aa, which was likely not sufficient to abolish PA-X activity ( Figure 1B ) (Jagger et 407 al., 2012) . The finding that truncating the X-ORF is sufficient to block PA-X activity in the virus 408 is also important, because single point mutations in the X-ORF sequence are less disruptive 409 changes than frameshifting mutations. Thus, viruses carrying X-ORF mutations could be better 410 tools for in vivo studies of PA-X function and IAV pathogenesis. rescue activity, suggesting that the X-ORF is needed for additional functions (Hayashi et al., 416 2016 ). Our BioID results corroborate this idea, since we did not only find proteins involved in 417 nuclear import, but identified many proteins with various roles in RNA metabolism. Also, by 418 examining the X-ORF in isolation, we likely excluded indirect interactions via RNA binding of 419 the RNase domain, as well as interactions that are important for PA rather than PA-X function. 420