title: The E3 ubiquitin ligase RNF185 facilitates the cGAS-mediated innate immune response.
abstract: The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression. Mechanistically, RNF185 specifically catalyzed the K27-linked poly-ubiquitination of cGAS, which promoted its enzymatic activity. Additionally, Systemic Lupus Erythematosus (SLE) patients displayed elevated expression of RNF185 mRNA. Collectively, this study uncovers RNF185 as the first E3 ubiquitin ligase of cGAS, shedding light on the regulation of cGAS activity in innate immune responses.
authors.affiliation: Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.|State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Liyuan
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Jiangning District, Nanjing, China.
authors.forename: Ze
authors.identifier: 0000-0001-5132-7335
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Zhongshi
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Lele
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lindi
authors.initials: L
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|School of Life Science and Technology, China Pharmaceutical University, Jiangning District, Nanjing, China.
authors.forename: Chen
authors.identifier: 0000-0002-9822-9393
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Molecular Nephrology and the Creative Training Center for Undergraduates, the Ministry of Education Key Laboratory of Laboratory Medical Diagnostics, the School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000276:immunology*; D009713:Nucleotidyltransferases / Q000276:immunology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000276:immunology*; D055815:Young Adult; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D024101:Mitochondrial Proteins; D009713:Nucleotidyltransferases; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; C569560:RNF185 protein, human; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase