The roles of the human CTD phosphatases in regulating gene expression

The production of messenger (m)RNA requires co-transcriptional processes such as capping, splicing, cleavage and polyadenylation. The carboxyl-terminal domain (CTD) of RNA polymerase II acts as a platform to recruit the proteins involved in co-transcriptional processes and therefore is involved in the crosstalk between transcription and co-transcriptional processes. The CTD is an unstructured domain composed of multiple tandem repeats of the consensus heptad sequence 1-Tyr-Ser-Pro-Thr-Ser-ProSer-7. Although phosphorylation of serine, tyrosine, and threonine residues by multiple CTD kinases has been described as being essential for the expression of most RNA polymerase II-transcribed genes, the removal of phosphorylation at the right time is likely to be as important as the addition of the modifications in the first place. My research project aims to understand the precise role(s) CTD phosphatases play in cellular processes, through modification of the CTD and other factors, the molecular mechanisms involved and how their activities are co-ordinated. As transcription is a fundamental process, a better understanding of the complex and dynamic molecular mechanisms involved in the transcription of human genes can help to understand and combat diseases such as cancer.