Rutkowski Andrzej J, Erhard Florian, L'Hernault Anne, Bonfert Thomas, Schilhabel Markus, Crump Colin, Rosenstiel Philip, Efstathiou Stacey, Zimmer Ralf, Friedel Caroline C, Dölken Lars
Division of Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Institut für Informatik, Ludwig-Maximilians-Universität München, Amalienstraße 17, 80333 München, Germany.
Nat Commun. 2015 May 20;6:7126. doi: 10.1038/ncomms8126.
Herpes simplex virus 1 (HSV-1) is an important human pathogen and a paradigm for virus-induced host shut-off. Here we show that global changes in transcription and RNA processing and their impact on translation can be analysed in a single experimental setting by applying 4sU-tagging of newly transcribed RNA and ribosome profiling to lytic HSV-1 infection. Unexpectedly, we find that HSV-1 triggers the disruption of transcription termination of cellular, but not viral, genes. This results in extensive transcription for tens of thousands of nucleotides beyond poly(A) sites and into downstream genes, leading to novel intergenic splicing between exons of neighbouring cellular genes. As a consequence, hundreds of cellular genes seem to be transcriptionally induced but are not translated. In contrast to previous reports, we show that HSV-1 does not inhibit co-transcriptional splicing. Our approach thus substantially advances our understanding of HSV-1 biology and establishes HSV-1 as a model system for studying transcription termination.
单纯疱疹病毒1型（HSV-1）是一种重要的人类病原体，也是病毒诱导宿主关闭的范例。在这里，我们表明，通过对新转录的RNA进行4sU标记和对裂解性HSV-1感染进行核糖体分析，可以在单一实验设置中分析转录和RNA加工的全局变化及其对翻译的影响。出乎意料的是，我们发现HSV-1触发了细胞基因而非病毒基因转录终止的破坏。这导致在聚腺苷酸化位点下游数万个核苷酸处进行广泛转录并进入下游基因，从而导致相邻细胞基因外显子之间出现新的基因间剪接。因此，数百个细胞基因似乎被转录诱导但未被翻译。与之前的报道相反，我们表明HSV-1不会抑制共转录剪接。因此，我们的方法极大地推进了我们对HSV-1生物学的理解，并将HSV-1确立为研究转录终止的模型系统。
