@article{RutkowskiErhardL'Hernaultetal.2015, author = {Rutkowski, Andrzej J. and Erhard, Florian and L'Hernault, Anne and Bonfert, Thomas and Schilhabel, Markus and Crump, Colin and Rosenstiel, Philip and Efstathiou, Stacey and Zimmer, Ralf and Friedel, Caroline C. and D{\"o}lken, Lars}, title = {Widespread disruption of host transcription termination in HSV-1 infection}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7126}, doi = {10.1038/ncomms8126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148643}, year = {2015}, abstract = {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.}, language = {en} } @article{HickeySridharWestermannetal.2012, author = {Hickey, Scott F. and Sridhar, Malathy and Westermann, Alexander J. and Qin, Qian and Vijayendra, Pooja and Liou, Geoffrey and Hammond, Ming C.}, title = {Transgene regulation in plants by alternative splicing of a suicide exon}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {10}, doi = {10.1093/nar/gks032}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134724}, pages = {4701-4710}, year = {2012}, abstract = {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.}, language = {en} }