The biological role of 2′- O -methylation of host and viral mRNA has remained elusive. Thiel and co-workers show that this modification modulates the induction of type I interferon and sensitivity to interferon. Supplementary information The online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users. The 5′ cap structures of higher eukaryote mRNAs have ribose 2′- O -methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2′- O -methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2′- O -methylation of mRNA remains elusive. Here we show that 2′- O -methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2′- O -methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2′- O -methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2′- O -methylation of mRNA suggests that RNA modifications such as 2′- O -methylation provide a molecular signature for the discrimination of self and non-self mRNA. Supplementary information The online version of this article (doi:10.1038/ni.1979) contains supplementary material, which is available to authorized users.
【저자키워드】 RNA modification, Innate immunity, Virus-host interactions,