Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response
cGAS, a DNA sensor in mammalian cells, catalyzes the generation of 2’-3’-cyclic AMP-GMP (cGAMP) once activated by the binding of free DNA. cGAMP can bind to STING, activating downstream TBK1-IRF-3 signaling to initiate the expression of type I interferons. Although cGAS has been considered a traditi...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:577cf92d29034ccfa068adc742c1124e2021-12-01T04:47:01ZRoles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response1664-322410.3389/fimmu.2021.741599https://doaj.org/article/577cf92d29034ccfa068adc742c1124e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.741599/fullhttps://doaj.org/toc/1664-3224cGAS, a DNA sensor in mammalian cells, catalyzes the generation of 2’-3’-cyclic AMP-GMP (cGAMP) once activated by the binding of free DNA. cGAMP can bind to STING, activating downstream TBK1-IRF-3 signaling to initiate the expression of type I interferons. Although cGAS has been considered a traditional DNA-binding protein, several lines of evidence suggest that cGAS is a potential RNA-binding protein (RBP), which is mainly supported by its interactions with RNAs, RBP partners, RNA/cGAS-phase-separations as well as its structural similarity with the dsRNA recognition receptor 2’-5’ oligoadenylate synthase. Moreover, two influential studies reported that the cGAS-like receptors (cGLRs) of fly Drosophila melanogaster sense RNA and control 3′-2′-cGAMP signaling. In this review, we summarize and discuss in depth recent studies that identified or implied cGAS as an RBP. We also comprehensively summarized current experimental methods and computational tools that can identify or predict RNAs that bind to cGAS. Based on these discussions, we appeal that the RNA-binding activity of cGAS cannot be ignored in the cGAS-mediated innate antiviral response. It will be important to identify RNAs that can bind and regulate the activity of cGAS in cells with or without virus infection. Our review provides novel insight into the regulation of cGAS by its RNA-binding activity and extends beyond its DNA-binding activity. Our review would be significant for understanding the precise modulation of cGAS activity, providing the foundation for the future development of drugs against cGAS-triggering autoimmune diseases such as Aicardi-Gourtières syndrome.Yuying MaYuying MaYuying MaXiaohui WangXiaohui WangXiaohui WangWeisheng LuoWeisheng LuoWeisheng LuoJi XiaoJi XiaoJi XiaoXiaowei SongXiaowei SongXiaowei SongYifei WangYifei WangYifei WangHanlin ShuaiZhe RenZhe RenZhe RenYiliang WangYiliang WangYiliang WangYiliang WangFrontiers Media S.A.articlecGASRNA-binding activityRNA-binding proteinphase-separated condensatesinnate antiviral responseImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
cGAS RNA-binding activity RNA-binding protein phase-separated condensates innate antiviral response Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
cGAS RNA-binding activity RNA-binding protein phase-separated condensates innate antiviral response Immunologic diseases. Allergy RC581-607 Yuying Ma Yuying Ma Yuying Ma Xiaohui Wang Xiaohui Wang Xiaohui Wang Weisheng Luo Weisheng Luo Weisheng Luo Ji Xiao Ji Xiao Ji Xiao Xiaowei Song Xiaowei Song Xiaowei Song Yifei Wang Yifei Wang Yifei Wang Hanlin Shuai Zhe Ren Zhe Ren Zhe Ren Yiliang Wang Yiliang Wang Yiliang Wang Yiliang Wang Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| description |
cGAS, a DNA sensor in mammalian cells, catalyzes the generation of 2’-3’-cyclic AMP-GMP (cGAMP) once activated by the binding of free DNA. cGAMP can bind to STING, activating downstream TBK1-IRF-3 signaling to initiate the expression of type I interferons. Although cGAS has been considered a traditional DNA-binding protein, several lines of evidence suggest that cGAS is a potential RNA-binding protein (RBP), which is mainly supported by its interactions with RNAs, RBP partners, RNA/cGAS-phase-separations as well as its structural similarity with the dsRNA recognition receptor 2’-5’ oligoadenylate synthase. Moreover, two influential studies reported that the cGAS-like receptors (cGLRs) of fly Drosophila melanogaster sense RNA and control 3′-2′-cGAMP signaling. In this review, we summarize and discuss in depth recent studies that identified or implied cGAS as an RBP. We also comprehensively summarized current experimental methods and computational tools that can identify or predict RNAs that bind to cGAS. Based on these discussions, we appeal that the RNA-binding activity of cGAS cannot be ignored in the cGAS-mediated innate antiviral response. It will be important to identify RNAs that can bind and regulate the activity of cGAS in cells with or without virus infection. Our review provides novel insight into the regulation of cGAS by its RNA-binding activity and extends beyond its DNA-binding activity. Our review would be significant for understanding the precise modulation of cGAS activity, providing the foundation for the future development of drugs against cGAS-triggering autoimmune diseases such as Aicardi-Gourtières syndrome. |
| format |
article |
| author |
Yuying Ma Yuying Ma Yuying Ma Xiaohui Wang Xiaohui Wang Xiaohui Wang Weisheng Luo Weisheng Luo Weisheng Luo Ji Xiao Ji Xiao Ji Xiao Xiaowei Song Xiaowei Song Xiaowei Song Yifei Wang Yifei Wang Yifei Wang Hanlin Shuai Zhe Ren Zhe Ren Zhe Ren Yiliang Wang Yiliang Wang Yiliang Wang Yiliang Wang |
| author_facet |
Yuying Ma Yuying Ma Yuying Ma Xiaohui Wang Xiaohui Wang Xiaohui Wang Weisheng Luo Weisheng Luo Weisheng Luo Ji Xiao Ji Xiao Ji Xiao Xiaowei Song Xiaowei Song Xiaowei Song Yifei Wang Yifei Wang Yifei Wang Hanlin Shuai Zhe Ren Zhe Ren Zhe Ren Yiliang Wang Yiliang Wang Yiliang Wang Yiliang Wang |
| author_sort |
Yuying Ma |
| title |
Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| title_short |
Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| title_full |
Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| title_fullStr |
Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| title_full_unstemmed |
Roles of Emerging RNA-Binding Activity of cGAS in Innate Antiviral Response |
| title_sort |
roles of emerging rna-binding activity of cgas in innate antiviral response |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/577cf92d29034ccfa068adc742c1124e |
| work_keys_str_mv |
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