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

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.

published proceedings

  • Nat Immunol

altmetric score

  • 14.35

author list (cited authors)

  • Zst, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B. W., Ziebuhr, J., ... Thiel, V.

citation count

  • 552

complete list of authors

  • Züst, Roland||Cervantes-Barragan, Luisa||Habjan, Matthias||Maier, Reinhard||Neuman, Benjamin W||Ziebuhr, John||Szretter, Kristy J||Baker, Susan C||Barchet, Winfried||Diamond, Michael S||Siddell, Stuart G||Ludewig, Burkhard||Thiel, Volker

publication date

  • January 2011