Degradation of WTAP blocks antiviral responses by reducing the m6A levels of IRF3 and IFNAR1 mRNA

N-6-methyladenosine (m(6)A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m(6)A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m(6)A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m(6)A modification in type I interferon (IFN-I) signaling are still largely unknown. Here, we reveal that WT1-associated protein (WTAP), one of the m(6)A "writers", is degraded via the ubiquitination-proteasome pathway upon activation of IFN-I signaling. With the degradation of WTAP, the m(6)A levels of IFN-regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP-IRF3/IFNAR1 axis may serve as negative feedback pathway to fine-tune the activation of IFN-I signaling, which highlights the roles of m(6)A in the antiviral response by dictating the fate of mRNAs associated with IFN-I signaling.