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.
Pubmed ID: 15208624 RIS Download
Mesh terms: Animals | Cell Line, Tumor | Cells, Cultured | DNA-Binding Proteins | Gene Expression Regulation | Genes, Reporter | Humans | Interferon Regulatory Factor-3 | Interferons | Mice | NF-kappa B | Promoter Regions, Genetic | Protein Structure, Tertiary | Proteins | RNA Helicases | RNA, Double-Stranded | RNA, Messenger | RNA, Small Interfering | Sequence Deletion | Signal Transduction | Transcription Factors | Transcriptional Activation | Viruses
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