RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element
文献类型：期刊论文
| Author | Yao, Yongxuan1,2; Yang, Bo1,2; Chen, Yingshan3,4; Wang, Hui3,4; Hu, Xue3; Zhou, Yuan3; Gao, Xiuzhu5; Lu, Mengji3,6; Niu, Junqi5; Wen, Zhe1 |
| Source | JOURNAL OF VIROLOGY
 |
| Issued Date | 2019-03-01 |
| Volume | 93Issue:6Pages:17 |
| Keyword | HBV polymerase HBV epsilon element RBM24 interaction pgRNA packaging |
| ISSN | 0022-538X |
| DOI | 10.1128/JVI.02161-18 |
| English Abstract | Encapsidation of pregenomic RNA (pgRNA) is a crucial step in hepatitis B virus (HBV) replication. Binding by viral polymerase (Pol) to the epsilon stem-loop (e) on the 5'-terminal region (TR) of pgRNA is required for pgRNA packaging. However, the detailed mechanism is not well understood. RNA-binding motif protein 24 (RBM24) inhibits core translation by binding to the 5'-TR of pgRNA. Here, we demonstrate that RBM24 is also involved in pgRNA packaging. RBM24 directly binds to the lower bulge of e via RNA recognition submotifs (RNPs). RBM24 also interacts with Pol in an RNA-independent manner. The alanine-rich domain (ARD) of RBM24 and the reverse transcriptase (RT) domain of Pol are essential for binding between RBM24 and Pol. In addition, overexpression of RBM24 increases Pol-e interaction, whereas RBM24 knockdown decreases the interaction. RBM24 was able to rescue binding between e and mutant Pol lacking e-binding activity, further showing that RBM24 mediates the interaction between Pol and e by forming a Pol-RBM24-c, complex. Finally, RBM24 significantly promotes the packaging efficiency of pgRNA. In conclusion, RBM24 mediates Pol-e interaction and formation of a Pol-RBM24-c complex, which inhibits translation of pgRNA and results in pgRNA packing into capsids/ virions for reverse transcription and DNA synthesis. IMPORTANCE Hepatitis B virus (HBV) is a ubiquitous human pathogen, and HBV infection is a major global health burden. Chronic HBV infection is associated with the development of liver diseases, including fulminant hepatitis, hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. A currently approved vaccine can prevent HBV infection, and medications are able to reduce viral loads and prevent liver disease progression. However, current treatments rarely achieve a cure for chronic infection. Thus, it is important to gain insight into the mechanisms of HBV replication. In this study, we found that the host factor RBM24 is involved in pregenomic RNA (pgRNA) packaging and regulates HBV replication. These findings highlight a potential target for antiviral therapeutics of HBV infection. |
| Funding Project | National Basic Research Priorities Program of China[2013CB911100] ; National Natural Science Foundation of China[31621061] ; National Natural Science Foundation of China[31770180] ; Youth Innovation Promotion Association, CAS[2016303] |
| WOS Research Area | Virology |
| Language | 英语 |
| WOS ID | WOS:000460292400049 |
| Publisher | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7031]  |
| Collection | 中国科学院武汉植物园 |
| Corresponding Author | Wu, Chunchen; Chen, Xinwen |
| Affiliation | 1.Guangzhou Women & Children Med Ctr, Joint Ctr Translat Precis Med, Guangzhou Inst Pediat, Guangzhou, Guangdong, Peoples R China 2.Chinese Acad Sci, Joint Ctr Translat Precis Med, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Jilin Univ, Dept Hepatol, Hosp 1, Changchun, Jilin, Peoples R China 6.Univ Hosp Essen, Inst Virol, Essen, Germany |
| Recommended Citation GB/T 7714 | Yao, Yongxuan,Yang, Bo,Chen, Yingshan,et al. RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element[J]. JOURNAL OF VIROLOGY,2019,93(6):17. |
| APA | Yao, Yongxuan.,Yang, Bo.,Chen, Yingshan.,Wang, Hui.,Hu, Xue.,...&Chen, Xinwen.(2019).RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element.JOURNAL OF VIROLOGY,93(6),17. |
| MLA | Yao, Yongxuan,et al."RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element".JOURNAL OF VIROLOGY 93.6(2019):17. |
入库方式： OAI收割
来源：武汉植物园
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