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Start Over Author "Hennig, Thomas" Journal nature communications
5 results on '"Hennig, Thomas"'

2. Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27.

Author

Wang, Xiuye, Hennig, Thomas, Whisnant, Adam, Erhard, Florian, Prusty, Bhupesh, Friedel, Caroline, Forouzmand, Elmira, Hu, William, Erber, Luke, Chen, Yue, Dölken, Lars, Sandri-Goldin, Rozanne, and Shi, Yongsheng

Subjects
Animals, Cell Line, Cleavage And Polyadenylation Specificity Factor, HeLa Cells, Herpes Simplex, Herpesvirus 1, Human, Host-Pathogen Interactions, Humans, Immediate-Early Proteins, RNA Processing, Post-Transcriptional, RNA, Messenger, Transcription Termination, Genetic
Abstract

Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3 processing factor CPSF. It thereby induces the assembly of a dead-end 3 processing complex, blocking mRNA 3 cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3 processing for viral and a subset of host transcripts. Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer.

Published
2020

4. Integrative functional genomics decodes herpes simplex virus 1

Author

Whisnant, Adam W., Jürges, Christopher S., Hennig, Thomas, Wyler, Emanuel, Prusty, Bhupesh, Rutkowski, Andrzej J., L’hernault, Anne, Djakovic, Lara, Göbel, Margarete, Döring, Kristina, Menegatti, Jennifer, Antrobus, Robin, Matheson, Nicholas J., Künzig, Florian W. H., Mastrobuoni, Guido, Bielow, Chris, Kempa, Stefan, Liang, Chunguang, Dandekar, Thomas, Zimmer, Ralf, Landthaler, Markus, Grässer, Friedrich, Lehner, Paul J., Friedel, Caroline C., Erhard, Florian, and Dölken, Lars

Published
2020
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5. Integrative functional genomics decodes herpes simplex virus 1

Author

Whisnant, Adam W, Jürges, Christopher S, Hennig, Thomas, Wyler, Emanuel, Prusty, Bhupesh, Rutkowski, Andrzej J, L'hernault, Anne, Djakovic, Lara, Göbel, Margarete, Döring, Kristina, Menegatti, Jennifer, Antrobus, Robin, Matheson, Nicholas J, Künzig, Florian WH, Mastrobuoni, Guido, Bielow, Chris, Kempa, Stefan, Liang, Chunguang, Dandekar, Thomas, Zimmer, Ralf, Landthaler, Markus, Grässer, Friedrich, Lehner, Paul J, Friedel, Caroline C, Erhard, Florian, Dölken, Lars, HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany., Whisnant, Adam W [0000-0003-2039-2809], Jürges, Christopher S [0000-0001-5617-6601], Wyler, Emanuel [0000-0002-9884-1806], Prusty, Bhupesh [0000-0001-7051-4670], Djakovic, Lara [0000-0002-9368-9403], Matheson, Nicholas J [0000-0002-3318-1851], Künzig, Florian WH [0000-0003-3730-3905], Mastrobuoni, Guido [0000-0003-4509-1295], Bielow, Chris [0000-0001-5756-3988], Kempa, Stefan [0000-0002-0696-9299], Liang, Chunguang [0000-0002-0305-2522], Dandekar, Thomas [0000-0003-1886-7625], Landthaler, Markus [0000-0002-1075-8734], Friedel, Caroline C [0000-0003-3569-4877], Erhard, Florian [0000-0002-3574-6983], Dölken, Lars [0000-0002-4651-3544], and Apollo - University of Cambridge Repository

Subjects
Gene Expression Regulation, Viral, Biological Products, Genes, Viral, viruses, Computational Biology, Genome, Viral, Genomics, Herpesvirus 1, Human, Fibroblasts, Article, Computational biology and bioinformatics, Open Reading Frames, Protein Domains, Cricetinae, Chlorocebus aethiops, Animals, Humans, Protein Isoforms, Herpes virus, Transcriptome, Ribosomes, Vero Cells
Abstract

The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution., Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.

Published
2019

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