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Widespread disruption of host transcription termination in HSV-1 infection

Please always quote using this URN: urn:nbn:de:bvb:20-opus-148643
  • 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 ofHerpes 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.show moreshow less

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Metadaten
Author: Andrzej J. Rutkowski, Florian Erhard, Anne L'Hernault, Thomas Bonfert, Markus Schilhabel, Colin Crump, Philip Rosenstiel, Stacey Efstathiou, Ralf Zimmer, Caroline C. Friedel, Lars Dölken
URN:urn:nbn:de:bvb:20-opus-148643
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Virologie und Immunbiologie
Language:English
Parent Title (English):Nature Communications
Year of Completion:2015
Volume:6
Issue:7126
Source:Nature Communications 6:7126 (2015). DOI: 10.1038/ncomms8126
DOI:https://doi.org/10.1038/ncomms8126
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:RNA polymerase II; alpha-globin; gene expression; herpes simplex virus; motif discovery; poly(A) site usage; pre-messenger RNA; regulatory protein ICP27; splicing inhibition; type 1 ICP27
Release Date:2018/11/15
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International