title: RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms.
abstract: Viral infection triggers induction of type I interferons (IFNs), which are critical mediators of innate antiviral immune response. Mediator of IRF3 activation (MITA, also called STING) is an adapter essential for virus-triggered IFN induction pathways. How post-translational modifications regulate the activity of MITA is not fully elucidated. In expression screens, we identified RING finger protein 26 (RNF26), an E3 ubiquitin ligase, could mediate polyubiquitination of MITA. Interestingly, RNF26 promoted K11-linked polyubiquitination of MITA at lysine 150, a residue also targeted by RNF5 for K48-linked polyubiquitination. Further experiments indicated that RNF26 protected MITA from RNF5-mediated K48-linked polyubiquitination and degradation that was required for quick and efficient type I IFN and proinflammatory cytokine induction after viral infection. On the other hand, RNF26 was required to limit excessive type I IFN response but not proinflammatory cytokine induction by promoting autophagic degradation of IRF3. Consistently, knockdown of RNF26 inhibited the expression of IFNB1 gene in various cells at the early phase and promoted it at the late phase of viral infection, respectively. Furthermore, knockdown of RNF26 inhibited viral replication, indicating that RNF26 antagonizes cellular antiviral response. Our findings thus suggest that RNF26 temporally regulates innate antiviral response by two distinct mechanisms.
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Mao-Tian
authors.initials: MT
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Yun-Hong
authors.initials: YH
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.affiliation: State Key Laboratory of Virology, Medical Research Institute, College of Life Sciences, Wuhan University, Wuhan, China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism*; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014775:Virus Activation; D014777:Virus Diseases / Q000276:immunology / Q000821:virology; D014779:Virus Replication; D014780:Viruses / Q000276:immunology*; D000099197:STING Protein
chemical_list: D000998:Antiviral Agents; D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; C494232:IRF3 protein, human; C427485:RNF26 protein, human; C532857:STING1 protein, human; D000099197:STING Protein