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

Publication

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

Journal Paper/Review - Jan 9, 2011

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

Citation

Züst R, Ludewig B, Siddell S, Diamond M, Barchet W, Baker S, Szretter K, Ziebuhr J, Neuman B, Maier R, Habjan M, Cervantes-Barragan L, Thiel V. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol 2011; 12:137-43.

Type

Journal Paper/Review (English)

Journal

Nat Immunol 2011; 12

Publication Date

Jan 9, 2011

Issn Electronic

1529-2916

Pages

137-43

Brief description/objective

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.