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Degradation of WTAP blocks antiviral responses by reducing the m 6 A levels of IRF3 and IFNAR1 mRNA
Author(s) -
Ge Yong,
Ling Tao,
Wang Yao,
Jia Xin,
Xie Xiongmei,
Chen Rong,
Chen Shangwu,
Yuan Shaochun,
Xu Anlong
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202052101
Subject(s) - degradation (telecommunications) , virology , biology , chemistry , microbiology and biotechnology , computer science , telecommunications
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.