G3BP1 promotes DNA binding and activation of cGAS

Liu, Zhao-Shan; Cai, Hong; Xue, Wei; Wang, Miao; Xia, Tian; Li, Wan-Jin; Xing, Jia-Qing; Zhao, Ming; Huang, Yanhong; Chen, Shuai; Wu, Shengming; Wang, Xinzheng; Liu, Xin; Pang, Xue; Zhang, Ziyu; Li, Tingting; Dai, Jiang; Dong, Fangting; Xia, Qing; Li, Ailing; Zhou, Tao; Liu, Zheng-gang; Zhang, Xuemin; Li, Tao

doi:10.1038/s41590-018-0262-4

Cited by 192 publications

(173 citation statements)

References 37 publications

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“…1C). While this manuscript was in revision, a report surfaced to indicate that G3BP1 could also act to promote c-GAS induction of ifn-b production (30). The authors also proposed that G3BP1 functioned independently of mammalian SG to promote DNA binding and activation of c-GAS.…”

Section: Discussionmentioning

confidence: 93%

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response

Kim

Sze

Lam

2019

Journal of Biological Chemistry

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RIG-I senses viral RNA in the cytosol and initiates host innate immune response by triggering the production of type 1 interferon. A recent RNAi knockdown screen yielded close to hundred host genes whose products affected viral RNA-induced IFN-␤ production and highlighted the complexity of the antiviral response. The stress granule protein G3BP1, known to arrest mRNA translation, was identified as a regulator of RIG-Iinduced IFN-␤ production. How G3BP1 functions in RIG-I signaling is not known, however. Here, we overexpress G3BP1 with RIG-I in HEK293T cells and found that G3BP1 significantly enhances RIG-I-induced ifn-b mRNA synthesis. More importantly, we demonstrate that G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1. Confocal microscopy studies also show G3BP1 co-localization with RIG-I and with infecting vesicular stomatitis virus in Cos-7 cells. Interestingly, immunoprecipitation studies using biotinlabeled viral dsRNA or poly(I⅐C) and cell lysate-derived or in vitro translated G3BP1 indicated that G3BP1 could directly bind these substrates and again via its RGG domain. Computational modeling further revealed a juxtaposed interaction between G3BP1 RGG and RIG-I RNA-binding domains. Together, our data reveal G3BP1 as a critical component of RIG-I signaling and possibly acting as a co-sensor to promote RIG-I recognition of pathogenic RNA.

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Section: Discussionmentioning

confidence: 93%

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response

Kim

Sze

Lam

2019

Journal of Biological Chemistry

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“…G3BP1 is a multifunctional protein that participates in many physiological processes, such as SG assembly, immune response, arteriosclerosis, and tumor promotion (24,26,27). In this study, we found that FMDV 3A interacted with G3BP1.…”

Section: Discussionmentioning

confidence: 99%

Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway

Yang

et al. 2020

J Virol

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Foot-and-mouth disease virus (FMDV) is one of the most notorious pathogens in the global livestock industry. To establish an infection, FMDV needs to counteract host antiviral responses. Several studies have shown how FMDV suppresses the type I interferon (IFN) response; however, whether FMDV modulates the integrated autophagy and innate immunity remains largely unknown. Here, the porcine Ras-GAP SH3-binding protein 1 (G3BP1) was shown to promote the retinoic acid-inducible gene I (RIG-I)-like helicase (RLH) signaling by upregulating the expression of RIG-I and melanoma differentiation-associated gene 5 (MDA5). FMDV nonstructural protein 3A interacted with G3BP1 to inhibit G3BP1 expression and G3BP1-mediated RLH signaling by upregulating the expression of autophagy-related protein LRRC25. In addition, 3A proteins of other picornaviruses, including Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also showed similar actions. Taking the data together, we elucidated, for the first time, a novel mechanism by which FMDV has evolved to inhibit IFN signaling and counteract host innate antiviral responses by autophagy. IMPORTANCE We show that foot-and-mouth disease virus (FMDV) 3A inhibits retinoic acid-inducible gene I (RIG-I)-like helicase signaling by degrading G3BP1 protein. Furthermore, FMDV 3A reduces G3BP1 by upregulating the expression of autophagy-related protein LRRC25. Additionally, other picornavirus 3A proteins, such as Seneca Valley virus (SVV) 3A, enterovirus 71 (EV71) 3A, and encephalomyocarditis virus (EMCV) 3A, also degrade G3BP1 by upregulating LRRC25 expression. This study will help us improve the design of current vaccines and aid the development of novel control strategies to combat FMD.

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“…Moreover, EGCG ameliorated experimental arthritis in mice by eliciting IDO-producing DCs, increasing the frequency of T reg cells and inducing the activation of the Nrf-2 antioxidant pathway [25]. A recent study showed that EGCG-mediated inhibition of G3BP1 provided a potential treatment for cGAS-related autoimmune diseases [26]. Overall, tea polyphenols provide a variety of biological actions such as anti-oxidant, anti-carcinogenic, anti-viral and anti-microbial activities [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a Real-World, Large-Scale Study

Jin¹,

Li²,

Gan³

et al. 2020

Ann Nutr Metab

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Introduction: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. Objectives: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. Methods: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. Results: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46–0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19–0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42–1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). Conclusion: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.

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G3BP1 promotes DNA binding and activation of cGAS

Cited by 192 publications

References 37 publications

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response

The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response

Foot-and-Mouth Disease Virus 3A Protein Causes Upregulation of Autophagy-Related Protein LRRC25 To Inhibit the G3BP1-Mediated RIG-Like Helicase-Signaling Pathway

Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a Real-World, Large-Scale Study

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