Retinoic acid-inducible gene I (RIG-I) is a pattern recognition receptor and is involved in the innate immune response against RNA viruses infection. Here, we demonstrate that the Ras-GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a positive regulator of the RIG-I-mediated signaling pathway. G3BP1-deficient cells inhibited RNA virus-triggered induction of downstream antiviral genes. Furthermore, we found that G3BP1 inhibited the replication of Sendai virus and vesicular stomatitis virus, indicating a positive regulation of G3BP1 to cellular antiviral responses. Mechanistically, G3BP1 formed a complex with RNF125 and RIG-I, leading to decreased RNF125 via its auto-ubiquitination; thus, promoting expression of RIG-I. Overall, the results suggest a novel mechanism for G3BP1 in the positive regulation of antiviral signaling mediated by RIG-I.

中文翻译：

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G3BP1通过积极调节RIG-I介导的细胞抗病毒反应来抑制RNA病毒复制。

维甲酸诱导基因I（RIG-I）是模式识别受体，参与针对RNA病毒感染的先天免疫应答。在这里，我们证明了Ras-GTPase激活蛋白SH3域结合蛋白1（G3BP1）充当RIG-I介导的信号通路的正向调节剂。G3BP1缺陷细胞抑制RNA病毒触发的下游抗病毒基因的诱导。此外，我们发现G3BP1抑制了仙台病毒和水泡性口炎病毒的复制，表明G3BP1对细胞抗病毒应答的正向调节。从机制上讲，G3BP1与RNF125和RIG-I形成复合物，通过其自身泛素化作用导致RNF125降低；因此，促进了RIG-I的表达。全面的，