Cytosolic viral sensor RIG-I is a 5'-triphosphate-dependent translocase on double-stranded RNA

Science. 2009 Feb 20;323(5917):1070-4. doi: 10.1126/science.1168352. Epub 2009 Jan 1.


Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cell Line
  • Cytosol / metabolism
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Kinetics
  • Nucleic Acid Heteroduplexes
  • Protein Structure, Tertiary
  • RNA / metabolism
  • RNA, Double-Stranded / metabolism*
  • RNA, Viral / metabolism
  • Receptors, Pattern Recognition / chemistry
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / metabolism*
  • Signal Transduction
  • Temperature


  • Nucleic Acid Heteroduplexes
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Pattern Recognition
  • RNA
  • Adenosine Triphosphate
  • DEAD-box RNA Helicases