RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate

Nat Immunol. 2009 Oct;10(10):1065-72. doi: 10.1038/ni.1779. Epub 2009 Jul 16.

Abstract

RNA is sensed by Toll-like receptor 7 (TLR7) and TLR8 or by the RNA helicases LGP2, Mda5 and RIG-I to trigger antiviral responses. Much less is known about sensors for DNA. Here we identify a novel DNA-sensing pathway involving RNA polymerase III and RIG-I. In this pathway, AT-rich double-stranded DNA (dsDNA) served as a template for RNA polymerase III and was transcribed into double-stranded RNA (dsRNA) containing a 5'-triphosphate moiety. Activation of RIG-I by this dsRNA induced production of type I interferon and activation of the transcription factor NF-kappaB. This pathway was important in the sensing of Epstein-Barr virus-encoded small RNAs, which were transcribed by RNA polymerase III and then triggered RIG-I activation. Thus, RNA polymerase III and RIG-I are pivotal in sensing viral DNA.

Publication types

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

MeSH terms

  • Animals
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / immunology*
  • DEAD-box RNA Helicases / metabolism
  • DNA, Viral / immunology*
  • DNA, Viral / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Humans
  • Interferon Type I / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Mice
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Poly dA-dT / immunology*
  • Poly dA-dT / metabolism
  • RNA Polymerase III / immunology*
  • RNA Polymerase III / metabolism
  • RNA, Double-Stranded / immunology
  • RNA, Viral / immunology
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic

Substances

  • DNA, Viral
  • Interferon Type I
  • NF-kappa B
  • RNA, Double-Stranded
  • RNA, Viral
  • Poly dA-dT
  • RNA Polymerase III
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases