The m <sup>6</sup> A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay
Daniel Macveigh-Fierro, Angelina M. Cicerchia, Ashley Cadorette, Vasudha Sharma, Mandy Muller
Abstract
Significance N6-methyladenosine (m 6 A) modifications play important roles in regulating RNA fate, in particular during viral infection. However, it remains unclear whether m 6 A modifications can also act in any antiviral capacity. During Kaposi’s sarcoma–associated herpesvirus infection, while most messenger RNA are degraded by the viral nuclease SOX, a subset of transcripts stringently escape degradation. Our study reveals that one such transcript, interleukin-6, acquires an m 6 A modification during the course of infection, which allows it to recruit the m 6 A reader YTHDC2. We show that this m 6 A modification along with the concomitant recruitment of YTHDC2 is essential to provide protection from SOX-induced decay. This suggests that m 6 A modifications can contribute to the host efforts to regain control of the gene expression environment.