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DOI | 10.1073/pnas.2019455118 |
Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs | |
Kim G.-W.; Siddiqui A. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:3 |
英文摘要 | Chronic hepatitis B virus (HBV) infections are one of the leading causes of cirrhosis and hepatocellular carcinoma. N6-methyladenosine (m6A) modification of cellular and viral RNAs is the most prevalent internal modification that occurs cotranscriptionally. Previously, we reported the dual functional role of m6A modification of HBV transcripts in the viral life cycle. Here, we show that viral HBV X (HBx) protein is responsible for the m6A modifications of viral transcripts. HBV genomes defective in HBx failed to induce m6A modifications of HBV RNAs during infection/transfection, while ectopic expression of HBx restores m6A modifications of the viral RNAs but not the mutant HBx carrying the nuclear export signal. Using chromatin immunoprecipitation assays, we provide evidence that HBx and m6A methyltransferase complexes are localized on the HBV minichromosome to achieve cotranscriptional m6A modification of viral RNAs. HBx interacts with METTL3 and 14 to carry out methylation activity and also modestly stimulates their nuclear import. This role of HBx in mediating m6A modification also extends to host phosphatase and tensin homolog (PTEN) mRNA. This study provides insight into how a viral protein recruits RNA methylation machinery to m6A-modify RNAs. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | N6-methyladenosine modification | METTL3/14 | hepatitis B virus | hepatitis B virus X protein | cotranscriptional modification |
语种 | 英语 |
scopus关键词 | 6 n methyladenosine; hepatitis B virus X protein; methyltransferase; RNA; virus RNA; Article; chromatin immunoprecipitation; ectopic expression; gene control; gene expression; hepatitis B; human; in vivo study; minichromosome; mutant; nonhuman; priority journal; protein function; protein modification; RNA methylation; RNA translation; viral RNA blood level; virus transcription |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America
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文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180965 |
作者单位 | Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San diego, CA 92093, United States |
推荐引用方式 GB/T 7714 | Kim G.-W.,Siddiqui A.. Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs[J],2021,118(3). |
APA | Kim G.-W.,&Siddiqui A..(2021).Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs.Proceedings of the National Academy of Sciences of the United States of America,118(3). |
MLA | Kim G.-W.,et al."Hepatitis B virus X protein recruits methyltransferases to affect cotranscriptional N6-methyladenosine modification of viral/host RNAs".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021). |
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