Seminar details

January 30, 2018, @ Small Lecture Theatre

Professor Jean Beggs , Edinburgh

Host: Vicky Cowling & David Lilley

Abstract

Splicing is the process of removing introns from precursor messenger RNAs, joining adjacent exons to produce spliced mRNA. There is extensive evidence that in both metazoans and yeast the process of splicing occurs as soon as the intron is transcribed and before transcription termination, i.e. co-transcriptionally. As a result, RNA polymerase II elongation rate can influence splicing. This coupling effect is not unidirectional. For example, my lab showed that splicing can affect transcription elongation, causing RNA polymerase to pause transiently while splicing takes place. More recently, links between splicing and chromatin modification have also become evident. To investigate the molecular basis of the interactions between these three important cellular process, my lab has developed methods to analyse transcription and splicing at high kinetic resolution and we combine this with rapid degradation of individual transcription, splicing and chromatin factors. Based on our results, we propose that transcription and chromatin may respond to signals from splicing fidelity checkpoints that may be related to decisions regarding alternative splicing events in higher eukaryotes.

Aslanzadeh, V., Huang, Y., Sanguinetti, G. and Beggs, J.D. Transcription Rate Strongly Affects Splicing Fidelity and Co-transcriptionality in Budding Yeast. Genome Research. In press.

Milligan L, et al. (2017) RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit. Elife pii: e27082. doi: 10.7554/eLife.27082.

Wallace, E. and Beggs, J.D. (2017) Extremely fast and incredibly close: co-transcriptional splicing in budding yeast. RNA, 23: 601-610. doi: 10.1261/rna.060830.117.

Barrass, J.D., Reid, J.E.A., Huang, Y., Hector, R.D., Sanguinetti, G., Beggs, J.D. and Granneman, S. (2015) Transcriptome-wide RNA processing kinetics revealed using extremely short 4tU labeling. Genome Biology 16: 282. doi: 10.1186/s13059-015-0848-1.

Alexander, R. and Beggs, J.D. (2010) Cross-talk in transcription, splicing and chromatin: who makes the first call? Biochem. Soc. Trans. 38:1251-6.