title: MicroRNA-939 restricts Hepatitis B virus by targeting Jmjd3-mediated and C/EBPα-coordinated chromatin remodeling.
abstract: Multi-layered mechanisms of virus host interaction exist for chronic hepatitis B virus (HBV) infection, which have been typically manifested at the microRNA level. Our previous study suggested that miRNA-939 (miR-939) may play a potential role in regulating HBV replication. Here we further investigated the mechanism by which miR-939 regulates HBV life cycle. We found that miR-939 inhibited the abundance of viral RNAs without direct miRNA-mRNA base pairing, but via host factors. Expression profiling and functional validation identified Jmjd3 as a target responsible for miR-939 induced anti-HBV effect. Jmjd3 appeared to enhance the transcription efficiency of HBV enhancer II/core promoter (En II) in a C/EBPα-dependent manner. However, the demethylase activity of Jmjd3 was not required in this process. Rather, Jmjd3's transactivation activity depended on its interaction with C/EBPα. This coordinated action further recruited the Brm containing SWI/SNF chromatin remodeling complex which promoted the transcription of HBV RNAs. Taken together, we propose that the miR-939-Jmjd3 axis perturbs the accessibility of En II promoter to essential nuclear factors (C/EBPα and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.
authors: Institute of Medical Microbiology and Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.|Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Cuncun
authors: C
authors: Chen
authors: Research Units, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Min
authors: M
authors: Wu
authors: Institute of Medical Microbiology and Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.|Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Wen
authors: W
authors: Zhang
authors: Department of Hepatology, Shanghai Public Health Clinical Center, Shanghai, China.
authors: Wei
authors: W
authors: Lu
authors: Department of Clinical Laboratory, Shanghai Public Health Clinical Center, Shanghai, China.
authors: Min
authors: M
authors: Zhang
authors: Department of Hepatology, Shanghai Public Health Clinical Center, Shanghai, China.
authors: Zhanqing
authors: Z
authors: Zhang
authors: Research Units, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors: Xiaonan
authors: X
authors: Zhang
authors: Institute of Medical Microbiology and Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.|Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Zhenghong
authors: Z
authors: Yuan
mesh_terms: D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012367:RNA, Viral / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D002868:Chromosomal Proteins, Non-Histone; C000604729:MIRN939 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human