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  - 
TY  - JOUR
A1  - Hickey, Scott F.
A1  - Sridhar, Malathy
A1  - Westermann, Alexander J.
A1  - Qin, Qian
A1  - Vijayendra, Pooja
A1  - Liou, Geoffrey
A1  - Hammond, Ming C.
T1  - Transgene regulation in plants by alternative splicing of a suicide exon
JF  - Nucleic Acids Research
N2  - Compared to transcriptional activation, other mechanisms of gene regulation have not been widely exploited for the control of transgenes. One barrier to the general use and application of alternative splicing is that splicing-regulated transgenes have not been shown to be reliably and simply designed. Here, we demonstrate that a cassette bearing a suicide exon can be inserted into a variety of open reading frames (ORFs), generating transgenes whose expression is activated by exon skipping in response to a specific protein inducer. The surprisingly minimal sequence requirements for the maintenance of splicing fidelity and regulation indicate that this splicing cassette can be used to regulate any ORF containing one of the amino acids Glu, Gln or Lys. Furthermore, a single copy of the splicing cassette was optimized by rational design to confer robust gene activation with no background expression in plants. Thus, conditional splicing has the potential to be generally useful for transgene regulation.
KW  - kingdom
KW  - pre-messenger RNA
KW  - gene expression
KW  - elements
KW  - decay
KW  - arabidopsis
KW  - eukaryotes
KW  - mechanisms
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134724
VL  - 40
IS  - 10
ER  -