中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
The 5 ' Untranslated Region of Human Bocavirus Capsid Transcripts Regulates Viral mRNA Biogenesis and Alternative Translation

文献类型:期刊论文

作者Guan, Wuxiang3; Huang, Min1; Wang, Hanzhong3; Xu, Huanzhou2,3; Chen, Zhen3; Hao, Sujuan2,3; Liu, Xiaoqian2,3
刊名JOURNAL OF VIROLOGY
出版日期2018-11-01
卷号92期号:21页码:16
ISSN号0022-538X
关键词HBoV1 alternative translation uATG 5 ' UTR
DOI10.1128/JVI.00443-18
英文摘要The capsid mRNA transcripts of human bocavirus 1 (HBoV1) can be generated by alternative splicing from the mRNA precursor transcribed from the P5 promoter. However, the alternative translation regulation mechanism of capsid mRNA transcripts is largely unknown. Here we report that the polycistronic capsid mRNA transcripts encode VP1, VP2, and VP3 in vitro and in vivo. The 5' untranslated regions (UTRs) of capsid mRNA transcripts, which consist of exons, affected not only the abundance of mRNA but also the translation pattern of capsid proteins. Further study showed that exons 2 and 3 were critical for the abundance of mRNA, while exon 4 regulated capsid translation. Alternative translation of capsid mRNA involved a leaky scan mechanism. Mutating the upstream ATGs (uATGs) located in exon 4 resulted in more mRNA transcripts polyadenylated at the proximal polyadenylation [(pA)p] site, leading to increased capsid mRNA transcripts. Moreover, uATG mutations induced more VP1 expression, while VP3 expression was decreased, which resulted in less progeny virus production. Our data show that the 5' UTR of HBoV1 plays a critical role in the modulation of mRNA abundance, alternative RNA processing, alternative translation, and progeny virus production. IMPORTANCE Alternative translation of HBoV1 capsid mRNAs is vital for the viral life cycle, as capsid proteins perform essential functions in genome packaging, assembly, and antigenicity. The 5' untranslated regions (UTRs) of capsid mRNAs are generated by alternative splicing, and they contain different exons. Our study shows that the 5' UTR not only modulates mRNA abundance but also regulates capsid expression. Two upstream ATGs (uATGs) that were upstream of the capsid translation initiation site in the 5' UTR were found to affect viral capsid mRNA polyadenylation, alternative translation, and progeny virus production. The results reveal that uATGs play an important role in the viral life cycle and represent a new layer to regulate HBoV1 RNA processing, which could be a target for gene therapy.
资助项目Ministry of Science and Technology of China[2016YFC1200400] ; Chinese Academy of Sciences[ZDRW-ZS-2016-4] ; Open Research Fund Program of the CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences[2015SPCAS002]
WOS研究方向Virology
语种英语
出版者AMER SOC MICROBIOLOGY
WOS记录号WOS:000447139100003
源URL[http://202.127.146.157/handle/2RYDP1HH/5881]  
专题中国科学院武汉植物园
通讯作者Guan, Wuxiang; Huang, Min
作者单位1.Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Lab Med, Wuhan, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Chinese Acad Sci, Ctr Emerging Infect Dis, Wuhan Inst Virol, Wuhan, Hubei, Peoples R China
推荐引用方式
GB/T 7714
Guan, Wuxiang,Huang, Min,Wang, Hanzhong,et al. The 5 ' Untranslated Region of Human Bocavirus Capsid Transcripts Regulates Viral mRNA Biogenesis and Alternative Translation[J]. JOURNAL OF VIROLOGY,2018,92(21):16.
APA Guan, Wuxiang.,Huang, Min.,Wang, Hanzhong.,Xu, Huanzhou.,Chen, Zhen.,...&Liu, Xiaoqian.(2018).The 5 ' Untranslated Region of Human Bocavirus Capsid Transcripts Regulates Viral mRNA Biogenesis and Alternative Translation.JOURNAL OF VIROLOGY,92(21),16.
MLA Guan, Wuxiang,et al."The 5 ' Untranslated Region of Human Bocavirus Capsid Transcripts Regulates Viral mRNA Biogenesis and Alternative Translation".JOURNAL OF VIROLOGY 92.21(2018):16.

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来源:武汉植物园

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