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

The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses
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DOI:
10.1038/ni1087
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发表时间:
2004-07-01
期刊:
影响因子:
30.5
通讯作者:
Fujita, T
Fujita, T
中科院分区:
医学1区
文献类型:
--
作者:
Yoneyama, M;Kikuchi, M;Fujita, T

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细胞内双链RNA (dsRNA)是许多病毒复制的主要标志。宿主机制检测dsRNA并启动抗病毒反应。在本报告中,我们通过功能筛选和实验鉴定了维甲酸诱导基因I (RIG-I),该基因编码含有caspase募集结构域的DExD/H盒RNA解旋酶,是dsrna诱导信号的重要调节因子。具有完整atp酶活性的解旋酶结构域负责dsrna介导的信号传导。caspase募集域传递“下游”信号,导致转录因子NF-kappaB和IRF-3的激活。随后这些因子的基因激活诱导了抗病毒功能,包括I型干扰素的产生。因此,rig - 1是检测和随后根除复制病毒基因组的关键。
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.