XRN1 is a Species-Specific Virus Restriction Factor in Yeasts

Paul A. Rowley; Brandon Ho; Sarah Bushong; Arlen Johnson; Sara L. Sawyer

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/069799 doi: bioRxiv preprint important for controlling the abundance of totivirus RNAs. We find that XRN1 and the 538 virus the best. The exact nature of the host-virus protein-protein interaction that is driving 539 this evolutionary arms race is not clear. To thwart XRN1, the totiviruses are known to 540 synthesize uncapped RNAs with an exposed 5' diphosphate, which is a suboptimal 541 substrate for Xrn1p-mediated decay [24] . Further, it has been shown that the totivirus 542 Gag protein has a cap-snatching activity that cleaves off caps from host mRNAs and 543 uses them to cap viral transcripts, protecting them from Xrn1p degradation [12, 14] . We 544 have found that Xrn1p interacts with L-A Gag, and that this interaction is not mediated by 545 the presence of single-stranded RNAs. What remains unknown is whether Xrn1p is 546 targeting Gag as part of the restriction mechanism, or whether Gag is targeting Xrn1p as 547 a counter defense. As we did not observe an obvious species-specific differences in the 548 interaction between Xrn1p and L-A Gag by coimmunoprecipitation, we cannot clearly 549 define the observed role of sequence variation in Xrn1p. This may be because of the 550 low sensitivity of our assay system, or because direct binding of Xrn1p by L-A Gag is 551 ubiquitous and that the rapid evolution of XRN1 results from another intriguing facet of 552 virus-host interaction and antagonism. However, we now know that the interaction 553 All rights reserved. No reuse allowed without permission.