RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate.
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.
Ablasser
Andrea
A
Institute for Clinical Chemistry and Pharmacology, University of Bonn, Bonn, Germany.
Bauernfeind
Franz
F
Hartmann
Gunther
G
Latz
Eicke
E
Fitzgerald
Katherine A
KA
Hornung
Veit
V
D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology* / Q000378:metabolism; D004279:DNA, Viral / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011067:Poly dA-dT / Q000276:immunology* / Q000378:metabolism; D012320:RNA Polymerase III / Q000276:immunology* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D004279:DNA, Viral; D007370:Interferon Type I; D016328:NF-kappa B; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D011067:Poly dA-dT; D012320:RNA Polymerase III; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases