Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5.

R. Zust, L. Cervantes-Barragan, M. Habjan, R. Maier, B.W. Neuman, John Ziebuhr, K.J. Szretter, S.C. Baker, W. Barchet, M.S. Diamond, S.G. Siddell, B. Ludewig, V. Thiel

Research output: Contribution to journalArticle

370 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)137-143
Number of pages7
JournalNature Immunology
Volume12(2)
Issue number2
DOIs
Publication statusPublished - Jan 2011

ASJC Scopus subject areas

  • Immunology

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    Zust, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B. W., Ziebuhr, J., Szretter, K. J., Baker, S. C., Barchet, W., Diamond, M. S., Siddell, S. G., Ludewig, B., & Thiel, V. (2011). Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nature Immunology, 12(2)(2), 137-143. https://doi.org/10.1038/ni.1979