RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway

Cell. 2009 Aug 7;138(3):576-91. doi: 10.1016/j.cell.2009.06.015. Epub 2009 Jul 23.


Type I interferons (IFNs) are important for antiviral and autoimmune responses. Retinoic acid-induced gene I (RIG-I) and mitochondrial antiviral signaling (MAVS) proteins mediate IFN production in response to cytosolic double-stranded RNA or single-stranded RNA containing 5'-triphosphate (5'-ppp). Cytosolic B form double-stranded DNA, such as poly(dA-dT)*poly(dA-dT) [poly(dA-dT)], can also induce IFN-beta, but the underlying mechanism is unknown. Here, we show that the cytosolic poly(dA-dT) DNA is converted into 5'-ppp RNA to induce IFN-beta through the RIG-I pathway. Biochemical purification led to the identification of DNA-dependent RNA polymerase III (Pol-III) as the enzyme responsible for synthesizing 5'-ppp RNA from the poly(dA-dT) template. Inhibition of RNA Pol-III prevents IFN-beta induction by transfection of DNA or infection with DNA viruses. Furthermore, Pol-III inhibition abrogates IFN-beta induction by the intracellular bacterium Legionella pneumophila and promotes the bacterial growth. These results suggest that RNA Pol-III is a cytosolic DNA sensor involved in innate immune responses.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Autoimmunity
  • Cell Line
  • Cell-Free System
  • Cytosol / immunology*
  • DNA / immunology*
  • DNA Viruses / immunology
  • Humans
  • Immunity, Innate*
  • Interferon-beta / immunology*
  • Interleukin-1beta / immunology
  • Legionella pneumophila / immunology
  • Mice
  • Polyphosphates / metabolism
  • RNA / chemistry
  • RNA / immunology
  • RNA / metabolism
  • RNA Polymerase III / immunology*
  • RNA Polymerase III / metabolism
  • RNA, Double-Stranded / metabolism
  • Signal Transduction*
  • Uridine Triphosphate / metabolism


  • Interleukin-1beta
  • Polyphosphates
  • RNA, Double-Stranded
  • RNA
  • Interferon-beta
  • Adenosine Triphosphate
  • DNA
  • RNA Polymerase III
  • triphosphoric acid
  • Uridine Triphosphate