RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; DEAD-box RNA Helicases; DNA, Viral; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Interferon Type I; Leukocytes, Mononuclear; Mice; NF-kappa B; Poly dA-dT; RNA Polymerase III; RNA, Double-Stranded; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic
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.
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Citation: Nat Immunol. 2009 Oct;10(10):1065-72. Epub 2009 Jul 16. Link to article on publisher's site