RNA polymerase II is a complex that catalyses the transcription of RNA from DNA. Some of these RNAs may go on to be used as instructions for protein synthesis in the cell. Others, called small nuclear RNAs, don’t code for protein but instead are involved in the processing of other RNA molecules. Activity of the RNA polymerase II is regulated by modifications to its carboxyl-terminal domain (CTD), a tail-like structure of one of the complex’s subunits. This can be achieved by kinases, such as the transcriptional cyclin-dependent kinases (CDKs), which add phosphate groups to the CTD. Meanwhile, phosphatases act antagonistically to remove these phosphate groups.
This Wellcome grant, which was awarded in April 2018, will fund research into the roles of transcriptional CDKs, and the CTD phosphatases, in regulation of RNA polymerase II-mediated transcription. As implied by the title of the grant, ‘Beyond the pol II CTD: the expanding roles of the pol II CTD modification enzymes’, the work will also go further by focusing on uncovering additional targets of these enzymes.
Shona expressed her excitement on hearing the good news, saying “Fantastic – now we can really get cracking!”
Previous work from Shona’s lab has shown that CDKs regulate not only transcription by polymerase II, but also influence the co-transcriptional processing of the transcribed RNA. In a multipronged approach, combining research into the role of CDKs in RNA polymerase II modification with a focus on different stages of the transcription cycle, co-transcriptional RNA processing and other potential CDK targets, the lab hopes to increase our understanding of the roles of these enzymes. This may have implications for the diagnosis and treatment of cancer and genetic diseases, since several of these kinases are mutated or mis-regulated in these conditions.
To read about research in the Murphy lab visit: http://murphy.path.ox.ac.uk
Written by Laura Hankins