The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses

M Yoneyama, M Kikuchi, T Natsukawa, N Shinobu… - Nature …, 2004 - nature.com
M Yoneyama, M Kikuchi, T Natsukawa, N Shinobu, T Imaizumi, M Miyagishi, K Taira, S Akira
Nature immunology, 2004nature.com
Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses.
Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we
identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase
that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced
signaling, as assessed by functional screening and assays. A helicase domain with intact
ATPase activity was responsible for the dsRNA-mediated signaling. The caspase …
Abstract
Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-κB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.
nature.com