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Significance 5-methylcytosine (m5C) is a common RNA methylation. However, its biological functions remain a mystery. Here, we discover that depletion of NSUN2, an m5C methyltransferase, leads to an enhanced type… Click to show full abstract
Significance 5-methylcytosine (m5C) is a common RNA methylation. However, its biological functions remain a mystery. Here, we discover that depletion of NSUN2, an m5C methyltransferase, leads to an enhanced type I interferon (IFN) response, which significantly inhibits replication of a wide range of RNA and DNA viruses in vitro. Notably, this m5C-mediated antiviral innate immunity is also conserved in an in vivo mouse model. Mechanistically, depletion of the m5C methyltransferase decreases the host RNA m5C methylome and enhances polymerase III–transcribed noncoding RNAs that are recognized by RIG-I to trigger enhanced type I IFN signaling. Our study reveals a role of m5C in regulating innate immunity and highlights m5C as a new target for development of broad-spectrum antiviral therapeutics.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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