Highlight talk – Theme: Systems
Abstract
Herpes simplex virus 1 (HSV-1) is an important human pathogen causing both common cold sores and life-threatening infections. Using next-generation sequencing technology, we performed a genome-wide screen of transcriptional (4sU-seq, RNA-seq) and translational (ribosome profiling) changes during the full course of HSV-1 lytic infection. Surprisingly, we found that HSV-1 specifically disrupts 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 neighboring cellular genes. In particular, this resulted in the seeming transcriptional induction of hundreds of cellular genes without corresponding translation. Interestingly, read-through transcription human genes recently has also been observed during osmotic stress, although not as extensive as during HSV-1 infection. Thus, our study not only establishes HSV-1 as a model system for studying transcription termination but highlights potential pitfalls in standard gene expression analysis.
Authors
Caroline C. Friedel, Institut fuer Informatik, Ludwig-Maximilians-Universitaet Muenchen, Germany
Andrzej Rutkowski, University of Cambridge, United Kingdom
Florian Erhard, Ludwig-Maximilians-Universitaet Muenchen, Germany
Anne L’Hernault, University of Cambridge, United Kingdom
Thomas Bonfert, Ludwig-Maximilians-Universitaet Muenchen, Germany
Markus Schilhabel, Christian-Albrechts-University Kiel, Germany
Colin Crump, University of Cambridge, United Kingdom
Philip Rosenstiel, Christian-Albrechts-University Kiel, Germany
Stacey Efstathiou, University of Cambridge, United Kingdom
Ralf Zimmer, LMU Munich, Germany
Lars Dölken, Julius-Maximilians-Universität Würzburg, Germany