The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
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-kappaB 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.
Yoneyama
Mitsutoshi
M
Department of Tumor Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
Kikuchi
Mika
M
Natsukawa
Takashi
T
Shinobu
Noriaki
N
Imaizumi
Tadaatsu
T
Miyagishi
Makoto
M
Taira
Kazunari
K
Akira
Shizuo
S
Fujita
Takashi
T
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3; D007372:Interferons / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014780:Viruses / Q000254:growth & development* / Q000276:immunology*
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; D011506:Proteins; C431552:RAI1 protein, human; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D007372:Interferons; D020365:RNA Helicases