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We employ C. elegans,  human cell lines and yeast to define evolutionary conserved mechanistic principles that underpin transcription and RNA biogenesis. We combine biochemical in vitro reconstitution, structural studies (Cryo-EM, x-ray crystallography and NMR in collaboration with groups of John Grimes and Jason Schnell, Oxford) and cutting edge functional genomics to test our hypotheses and further uncover the mechanisms that regulate gene expression programs.  

We are focused on two central questions:

1. How is mRNA processing coupled to RNA polymerase II transcription?

To form functional mRNA molecules that can be translated in the cytoplasm to proteins, mRNAs are subjected to extensive processing such as capping, splicing and 3’end cleavage and polyadenylation during Pol II transcription. Cleavage of nascent RNA by the 3'end processing machineries-Cleavage and Polyadenylation machinery and the Integrator determines properties and function of the synthesized RNA. We aim to uncover how activity of the 3'end processing machineries is controlled during  transcription and how post-translational modifications such as phosphorylation of transcription factors contribute to the regulation of the 3'end processing of nascent RNA.