A mechanistic understanding of the splicing and transcription cross-talk
Dr. Tugce Aktas
The human genome contains ~20.000 protein-coding genes, more than 95% of which contain introns that are removed by the Spliceosome in a highly regulated manner. The bulk of splicing happens co-transcriptionally while RNA polymerase II is still on the template DNA. Splicing is not an "all or none" event, inclusion or exclusion of exons is regulated by the composition of RNA-binding proteins binding to them, which can also be regulated by post-translational modifications that themselves are regulated by both intracellular and extracellular cues. In addition, the speed of RNA polymerase II can also affect splice-site choices, indicating a cross-talk between RNAPII and RNA-binding proteins that assemble on the nascent RNA.
In this project, the PhD candidate will investigate this cross-talk from the perspective of RNA-binding proteins. The key questions that will be addressed are: Can RNA-binding proteins affect the speed and processivity of RNAPII? If so, how is the information on nascent RNA relayed to RNAPII during transcription? And how much of this process is regulated by concentration-driven compartmentalization?
An ideal PhD candidate should have a relevant background in biochemistry and functional genomics tools. Experience with computational analysis of high throughput sequencing data is a plus.
For more information visit the website of the Aktas lab (Quantitative RNA biology).