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The role of RNA processing factors and nascent RNA in the regulation of transcription elongation

Dr Victoria BEGLEY
Regulatory Genomics Research Group, UCL Cancer Institute, London

Friday, November 8th 2019 - 2 p.m. - Meeting room 4004, IGBMC
Hosted by Laszlo TORA

Cross-talk between the transcription and mRNA degradation machineries is necessary for maintaining mRNA homeostasis, however, the mechanism by which it occurs is not well understood. During my PhD, I unravelled some of the mechanisms through which this cross-talk occurs in Saccharomyces cerevisiae. Using glucose-mediated repression of the GAL1 gene as an experimental approach, I determined the role of a select set of regulatory proteins through genetic analysis. This led to the conclusion that two mRNA degradation factors, Xrn1 and Ccr4-Not, regulated RNA polymerase II (Pol II) elongation. Since the role of Xrn1 in cross-talk has been controversial, I also analysed this mutant in more detail using CRAC-seq. I found significant effects of Xrn1 perturbation on Pol II profiles across the genome, in both the 5’ and 3’ ends of gene bodies, confirming its role in regulating transcriptional elongation. Following this work, I decided to continue studying the role of RNA in transcription but to transition to working with mammalian systems. My proposed postdoc work in Professor Jenner’s lab focuses on the possible role of nascent pre-mRNA in the recruitment of P-TEFb (a transcription elongation factor) to genes in embryonic stem cells and other cell types. P-TEFb is held in a repressed state on chromatin by binding to the 7SK ribonucleoprotein complex. I hypothesize that nascent pre-mRNA plays a direct role in regulating transcriptional elongation and coordinating RNA processing by recruiting P-TEFb from 7SK to genes activated during cell differentiation.

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