RIG-I: tri-ing to discriminate between self and non-self RNA

Trends Immunol. 2007 Apr;28(4):147-50. doi: 10.1016/j.it.2007.02.002. Epub 2007 Feb 16.


The ability to distinguish foreign nucleic acids from abundant self nucleic acids is essential to protect the host from invading pathogens. Several innate immune surveillance systems have evolved to detect nucleic acids and trigger cellular responses to eliminate foreign invaders. For RNA recognition, these include double stranded (ds)RNA-dependent protein kinase, Toll-like receptor (TLR)3, TLR7, TLR8, retinoic acid-inducible gene (RIG)-I and melanoma differentiation-associated gene 5. In the case of the nucleic-acid-sensing TLRs, endosomal localization is thought to be crucial for providing self versus non-self discrimination. For RNA-sensing in the cytoplasm, RIG-I was recently shown to detect and directly bind to the 5'-end of certain viral RNA genomes, specifically, to a 5'-triphosphate group. Such 5'-triphosphates are generally removed from, or masked on, host RNA species, thereby remaining silent to innate immunity and providing a structural basis for the distinction between self and non-self RNA. The mechanisms by which MDA5 senses RNA are unclear at present but seem to involve the sensing of dsRNA structures.

Publication types

  • Review

MeSH terms

  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / physiology*
  • Genome, Viral / genetics
  • Genome, Viral / immunology
  • Humans
  • Immunologic Surveillance / genetics
  • RNA, Viral / immunology
  • RNA, Viral / metabolism*
  • Receptors, Immunologic
  • Self Tolerance / genetics
  • Self Tolerance / immunology*


  • RNA, Viral
  • Receptors, Immunologic
  • DDX58 protein, human
  • Ddx58 protein, mouse
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases