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

Identifieur interne : 001832 ( Main/Exploration ); précédent : 001831; suivant : 001833

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

Auteurs : Andrea Ablasser [Allemagne] ; Franz Bauernfeind [Allemagne] ; Gunther Hartmann [Allemagne] ; Eicke Latz [États-Unis] ; Katherine A. Fitzgerald [États-Unis] ; Veit Hornung [Allemagne]

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RBID : ISTEX:48BF4DE151160F7EC852D40765576DF0A408F2EB

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-κB. 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.
After binding double-stranded RNA, RIG-I induces production of type 1 interferon. Hornung and colleagues find that RIG-I detects viral DNA via double-stranded RNA intermediates generated by RNA polymerase III.

Url:
DOI: 10.1038/ni.1779


Affiliations:


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