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

A Ablasser, F Bauernfeind, G Hartmann, E Latz… - Nature …, 2009 - nature.com
Nature immunology, 2009nature.com
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 …
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.
nature.com