title: The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination.
abstract: The signaling adaptor MAVS forms prion-like aggregates to activate an innate antiviral immune response after viral infection. However, the molecular mechanisms that regulate MAVS aggregation are poorly understood. Here we identified TRIM31, an E3 ubiquitin ligase of the TRIM family of proteins, as a regulator of MAVS aggregation. TRIM31 was recruited to mitochondria after viral infection and specifically regulated antiviral signaling mediated by RLR pattern-recognition receptors. TRIM31-deficient mice were more susceptible to infection with RNA virus than were wild-type mice. TRIM31 interacted with MAVS and catalyzed the Lys63 (K63)-linked polyubiquitination of Lys10, Lys311 and Lys461 on MAVS. This modification promoted the formation of prion-like aggregates of MAVS after viral infection. Our findings reveal new insights in the molecular regulation of MAVS aggregation and the cellular antiviral response through TRIM31-mediated K63-linked polyubiquitination of MAVS.
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Honghai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Guanhua
authors.initials: G
authors.lastname: Song
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Xueer
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, Jinan, China.
authors.forename: Chengjiang
authors.initials: C
authors.lastname: Gao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D007113:Immunity, Innate / Q000235:genetics; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000276:immunology*; D011940:Receptor Aggregation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination / Q000235:genetics; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008239:Lysine; D009687:Nuclear Proteins; D011328:Prions; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C512612:MAVS protein, mouse; C543617:TRIM31 protein, mouse