Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5

J Exp Med. 2008 Jul 7;205(7):1601-10. doi: 10.1084/jem.20080091.

Abstract

The ribonucleic acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons. Although 5'-triphosphate single-stranded RNA is a RIG-I ligand, the role of RIG-I and MDA5 in double-stranded (ds) RNA recognition remains to be characterized. In this study, we show that the length of dsRNA is important for differential recognition by RIG-I and MDA5. The MDA5 ligand, polyinosinic-polycytidylic acid, was converted to a RIG-I ligand after shortening of the dsRNA length. In addition, viral dsRNAs differentially activated RIG-I and MDA5, depending on their length. Vesicular stomatitis virus infection generated dsRNA, which is responsible for RIG-I-mediated recognition. Collectively, RIG-I detects dsRNAs without a 5'-triphosphate end, and RIG-I and MDA5 selectively recognize short and long dsRNAs, respectively.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Interferon-Induced Helicase, IFIH1
  • Mice
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Vesicular Stomatitis / genetics
  • Vesicular Stomatitis / metabolism*
  • Vesiculovirus / genetics
  • Vesiculovirus / metabolism*

Substances

  • RNA, Double-Stranded
  • RNA, Viral
  • Ddx58 protein, mouse
  • Ifih1 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1