期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep35974
关键词
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资金
- National Science and Technology Major Project of China [2016ZX10002010-003]
- National Natural Science Foundation [81201278]
- National Key Basic Research Program of China [2012CB519005]
- National Health and Family Planning Commission [201302010]
- German Research Foundation [SFB/Transregio TRR60]
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/EBP alpha-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/EBP alpha. 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/EBPc and SWI/SNF complex) therefore leading to compromised viral RNA synthesis and hence restricted viral multiplication.
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