Decoding human cytomegalovirus.

Decoding human cytomegalovirus.
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DOI:
10.1126/science.1227919
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发表时间:
2012-11-23
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Weissman JS
Weissman JS
中科院分区:
其他
文献类型:
--
作者:
Stern-Ginossar N;Weisburd B;Michalski A;Le VT;Hein MY;Huang SX;Ma M;Shen B;Qian SB;Hengel H;Mann M;Ingolia NT;Weissman JS

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人类巨细胞病毒(HCMV)基因组在20年前就已完成测序。然而,像其他复杂病毒一样,我们对其蛋白质编码潜能的了解还远远不够完整。在此,我们利用核糖体图谱分析和转录本分析,通过实验确定HCMV的翻译产物,并追踪它们的时间表达情况。我们鉴定出了数百个此前未被识别的开放阅读框,并通过质谱分析确认了其中一部分。我们发现,对可变转录起始位点的调控使用在实现对HCMV蛋白质表达的严格时间控制以及允许从单个基因组位点产生多种不同多肽方面发挥着广泛的作用。我们的研究结果揭示了HCMV编码能力的一种意想不到的复杂性,并阐明了转录起始位点的调控变化在产生这种复杂性方面的作用。
The human cytomegalovirus (HCMV) genome was sequenced 20 years ago. However, like other complex viruses, our understanding of its protein coding potential is far from complete. Here we use ribosome profiling and transcript analysis to experimentally define the HCMV translation products and follow their temporal expression. We identified hundreds of previously unidentified open reading frames and confirmed a fraction by mass spectrometry. We found that regulated use of alternative transcript start sites plays a broad role in enabling tight temporal control of HCMV protein expression and allowing multiple distinct polypeptides to be generated from a single genomic locus. Our results reveal an unanticipated complexity to the HCMV coding capacity and illustrate the role of regulated changes in transcript start sites in generating this complexity.
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