Description of research and teaching

Controlling Transcription Elongation by RNA polymerase II: mechanisms, disease and development

We are investigating the fundamental mechanisms of metazoan gene transcription by RNA polymerase II (RNAPII). In particular, we are studying the regulatory factors that modulate RNAPII transcription at the level of elongation, which has been recognized only recently as a major rate-limiting step in gene expression. Our work is focused mainly on the key cyclin-dependent kinases that stimulate RNAPII elongation and phosphorylate the C-terminal domain of the biggest subunit of RNAPII, Rbp1, at serine 2 (Ser2-P CTD). By using biochemistry, genetics and the tools of systems biology, we are aiming to understand mechanisms that enable the function of elongation kinases as well as biological processes that are controlled by them. Because transcription elongation can be intimately connected to pre-mRNA processing in the course of transcription via Ser2-P CTD, we are also studying how elongation kinases affect mRNA maturation events such as alternative splicing. Of note, an important aspect of our work is to uncover how deregulation of RNAPII elongation control contributes to the onset of deadly diseases, including cancer. Finally, revealing the significance of transcription elongation kinases in embryonic development remains a pressing issue in our research group.