The thermodynamic basis for viral RNA detection by the RIG-I innate immune sensor

J Biol Chem. 2012 Dec 14;287(51):42564-73. doi: 10.1074/jbc.M112.385146. Epub 2012 Oct 10.


RIG-I is a cytoplasmic surveillance protein that contributes to the earliest stages of the vertebrate innate immune response. The protein specifically recognizes 5'-triphosphorylated RNA structures that are released into the cell by viruses, such as influenza and hepatitis C. To understand the energetic basis for viral RNA recognition by RIG-I, we studied the binding of RIG-I domain variants to a family of dsRNA ligands. Thermodynamic analysis revealed that the isolated RIG-I domains each make important contributions to affinity and that they interact using different strategies. Covalent linkage between the domains enhances RNA ligand specificity while reducing overall binding affinity, thereby providing a mechanism for discriminating virus from host RNA.

MeSH terms

  • Humans
  • Immunity, Innate*
  • Kinetics
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Double-Stranded / metabolism*
  • RNA, Viral / metabolism*
  • Substrate Specificity
  • Thermodynamics
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*


  • RNA, Double-Stranded
  • RNA, Viral
  • RNF135 protein, human
  • Ubiquitin-Protein Ligases