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.
Conflict of interest statement
The authors declare that they have no conflict of interest.
A GTPase-activating protein-binding protein (G3BP1)/antiviral protein relay conveys arteriosclerotic Wnt signals in aortic smooth muscle cells.J Biol Chem. 2018 May 25;293(21):7942-7968. doi: 10.1074/jbc.RA118.002046. Epub 2018 Apr 6. J Biol Chem. 2018. PMID: 29626090 Free PMC article.
Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway.J Virol. 2020 Mar 31;94(8):e02086-19. doi: 10.1128/JVI.02086-19. Print 2020 Mar 31. J Virol. 2020. PMID: 31996428 Free PMC article.
The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response.J Biol Chem. 2019 Apr 19;294(16):6430-6438. doi: 10.1074/jbc.RA118.005868. Epub 2019 Feb 25. J Biol Chem. 2019. PMID: 30804210 Free PMC article.
Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity.Front Immunol. 2017 Jan 3;7:662. doi: 10.3389/fimmu.2016.00662. eCollection 2016. Front Immunol. 2017. PMID: 28096803 Free PMC article. Review.
RIG-I in RNA virus recognition.Version 2. Virology. 2015 May;479-480:110-21. doi: 10.1016/j.virol.2015.02.017. Epub 2015 Mar 5. Virology. 2015. PMID: 25749629 Free PMC article. Review.
- Akira S. TLR signaling. Curr. Top. Microbiol Immunol. 2006;311:1–16. - PubMed
- 17JR5RA323/Gansu Science and Technology Department (Science and Technology Department of Gansu Province)/International
- U1501213/National Natural Science Foundation of China (National Science Foundation of China)/International
- 31672585/National Natural Science Foundation of China (National Science Foundation of China)/International
- U1501213/Chinese Ministry of Science and Technology | Department of S and T for Social Development (Department of S&T for Social Development)/International
- Y2017JC55/Chinese Academy of Agricultural Sciences (CAAS)/International