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

Publikation

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

Wissenschaftlicher Artikel/Review - 09.01.2011

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

Zitation

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.

Art

Wissenschaftlicher Artikel/Review (Englisch)

Zeitschrift

Nat Immunol 2011; 12

Veröffentlichungsdatum

09.01.2011

eISSN (Online)

1529-2916

Seiten

137-43

Kurzbeschreibung/Zielsetzung

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.