RNA Polymerase II CTD readers in gene expression regulation

Year of award: 2016


  • Dr Pawel Grzechnik

    University of Birmingham

Project summary

Gene expression is the most strictly controlled process in a living cell. It involves transcription of genetic information encoded in DNA to RNA. This is followed by RNA processing or degradation. Any defect in this process may lead to developmental defects, ineffective stress responses, premature ageing, carcinogenesis and ultimately cell death.

In eukaryotic cells, major RNA metabolism regulatory mechanisms are mediated by the RNA Polymerase II C-terminal domain (CTD). Phosphorylation of CTD constitutes ‘the CTD code’, which is believed to define the recruitment of specific factors (‘CTD readers’) mediating all steps in the transcriptional cycle as well as RNA processing and degradation. In human cells, deregulations of processes mediated by CTD readers are directly associated with cancer and other genetic disorders. Although CTD readers have emerged as central players regulating nuclear RNA metabolism, their functions are still not fully uncovered.

My goal is to elucidate how these fundamental factors ‘police’ RNA by regulating the transcriptional cycle, transcription termination and the stress response. This knowledge will contribute to our understanding of fundamental processes facilitating normal cellular lifespan at the molecular level.