Transcription termination: interconnections between transcription and pre-mRNA processing. (360G-Wellcome-078483_Z_05_Z)

All stages of gene expression from nuclear transcription to cytoplasmic translation are intimately connected. We demonstrated two decades ago that the pre-mRNA processing reaction of 3' end cleavage/polyadenylation connects to transcription elongation/ termination. Since then all mRNA processing reactions have been shown to occur co-transcriptionally, affording tight gene regulation. We will extend our understanding of these connections to an advanced stage. We aim to determine how the chromatin template influences the connection between transcription and mRNA processing. We will then concentrate on dissecting the different ways transcription termination occurs in both yeast and mammalian genes. We will also extend our understanding of how termination feeds back to reinitiation of transcription by analysis of recently discovered gene loops. Our approach of comparing the mechanism of RNA polymerase I and II transcriptional termination in yeast as well as comparing RNA polymerase II termination between yeast and mammalian cells has already generated new data (see Appendix Figure 1-5). We now plan to fully dissect the molecular mechanism and biological significance of eukaryotic transcriptional termination. As such we are investigating fundamental aspects of eukaryotic gene expression, an essential approach to interpret the significance of the human genome sequence.