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 |
DOI | 10.1128/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. |
入库方式: OAI收割
来源:武汉植物园
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