NSUN2-mediated M⁵c methylation of IRF3 mRNA negatively regulates type I interferon responses during various viral infections.

ABSTRACT: 5-Methylcytosine (m⁵C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m⁵C methyltransferase, negatively regulates type I interferon responses during various viral infections, including SARS-CoV-2. NSUN2 specifically mediates m⁵C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 enhanced type I interferon and downstream ISGs during various viral infection in vitro. And in vivo, the anti

SUBMITTER: Wang H 

PROVIDER: S-EPMC9946332 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature