Jane Mellor - Gene Regulation: Sense, antisense and non-coding transcription and transcript fate

Eukaryotic genomesare pervasively transcribed in gene rich regions leading to the production of avariety of transcripts including coding pre-mRNAs, antisense transcripts, di-cistronic transcripts and other long non-coding transcripts. We havediscovered that many transcripts are unstable, or are retained in thenucleus, raising interesting questions about how the differential fate oftranscripts is determined. Using Saccharomyces cerevisiae as a model system, firstwe show that the Isw1 chromatin remodelling ATPase retains poorly processedtranscripts in the nucleus. Second, we have developed a novel nucleotideresolution, strand-specific technique to map the association oftranscription elongation factors with RNA polymerase II. We show thatlevels of Paf1 on RNA polymerase II contribute to the fate of the encodedtranscripts, with low levels associated with nuclear retention oftranscripts. Finally using mathematical modelling, we show how antisensetranscription influences sense transcription and transcripts.