Defining the functional determinants for RNA surveillance by RIG-I

EMBO Rep. 2013 Sep;14(9):772-9. doi: 10.1038/embor.2013.108. Epub 2013 Jul 30.


Retinoic acid-inducible gene-I (RIG-I) is an intracellular RNA sensor that activates the innate immune machinery in response to infection by RNA viruses. Here, we report the crystal structure of distinct conformations of a RIG-I:dsRNA complex, which shows that HEL2i-mediated scanning allows RIG-I to sense the length of RNA targets. To understand the implications of HEL2i scanning for catalytic activity and signalling by RIG-I, we examined its ATPase activity when stimulated by duplex RNAs of varying lengths and 5' composition. We identified a minimal RNA duplex that binds one RIG-I molecule, stimulates robust ATPase activity, and elicits a RIG-I-mediated interferon response in cells. Our results reveal that the minimal functional unit of the RIG-I:RNA complex is a monomer that binds at the terminus of a duplex RNA substrate. This behaviour is markedly different from the RIG-I paralog melanoma differentiation-associated gene 5 (MDA5), which forms cooperative filaments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Amino Acid Sequence
  • Catalytic Domain
  • HEK293 Cells
  • Humans
  • Molecular Docking Simulation*
  • Molecular Sequence Data
  • Protein Binding
  • RNA / metabolism*
  • RNA Helicases / chemistry*
  • RNA Helicases / metabolism


  • Adenosine Diphosphate
  • RNA
  • RNA Helicases