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, 12:137-143)

報告日期: 2011/03/08
報告時間: 17:10/18:00
報告學生: 陳冠儒
講評老師: 黎煥耀

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000308-1.pdf

Ribose 2-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
Roland Züst, Luisa Cervantes-Barragan, Matthias Habjan, Reinhard Maier, Benjamin W Neuman, John Ziebuhr, Kristy J Szretter, Susan C Baker, Winfried Barchet, Michael S Diamond, Stuart G Siddell, Burkhard Ludewig& Volker Thiel
Nature Immunology 12, 137-143 (2011)
Speaker : Kuan-Ru Chen (陳冠儒)
Commentator:Huan-Yao Lei, Ph.D (黎煥耀)
Time: 17:10-18:00
Place: 602
The innate immune system uses pattern recognition receptors to detect viral infection and triggers antiviral response. RIG-I and MDA5 detect cytoplasmic RNA during viral infection and further discriminate between self and non-self RNA. Eukaryotic mRNA is methylated at the N7 of the capping guanosine and the 2’-O -methyl group of the penultimate nucleotide, which is not detected by RIG-I and MDA5. Pervious studies indicated that many viruses have methyltransferase to modify their RNA in order to evade innate immune recognition. However, the relationship between 2′-O-methylation of viral mRNA and host innate immune system remains unclear. Here this work first found that that non-methylated viral mRNA induced higher type I interferon expression through the cytoplasmic RNA sensor MDA5. In addition, 2′-O-methyltransferase mutants of human and mouse coronaviruses were more sensitive to type I interforn pretreatment. The replication of these viruses was restricted by the interferon-induced protein IFIT1. Furthermore, the in vivo study demonstrated that 2′-O-methylation of viral RNA contributes to evasion of innate immune system. Thus, this study indicated that 2′-O-methylation of viral mRNA mimics the self RNA to evade innate immune system, and suggest 2′-O-methylation in RNA serves as the molecular signature to distinguish self from non-self RNA. 
Daffis, S. et al. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 468, 452–456 (2010).