TY  - JOUR
A1  - Rutkowski, Andrzej J.
A1  - Erhard, Florian
A1  - L'Hernault, Anne
A1  - Bonfert, Thomas
A1  - Schilhabel, Markus
A1  - Crump, Colin
A1  - Rosenstiel, Philip
A1  - Efstathiou, Stacey
A1  - Zimmer, Ralf
A1  - Friedel, Caroline C.
A1  - Dölken, Lars
T1  - Widespread disruption of host transcription termination in HSV-1 infection
JF  - Nature Communications
N2  - 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.
KW  - herpes simplex virus
KW  - RNA polymerase II
KW  - gene expression
KW  - alpha-globin
KW  - motif discovery
KW  - regulatory protein ICP27
KW  - poly(A) site usage
KW  - pre-messenger RNA
KW  - splicing inhibition
KW  - type 1 ICP27
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148643
VL  - 6
IS  - 7126
ER  -