The subject of this research project is the structural molecular biology of RNA 3'-end processing and of the integration with transcription and RNA export. RNA processing reactions can be reconstituted in vitro, but they occur more efficiently in the cell because they are closely integrated with transcription. How these biological processes are regulated and integrated with each other remains unclear at the molecular level and poorly understood structurally. Thus, dissecting how transcription and RNA export are coupled with processing at the molecular and structural level, as we propose to do, is an essential step to understanding how gene expression pathways are integrated and regulated. In order to address these biological problems, we propose to study: (1) the molecular basis for the specific recognition of different phosphorylated forms of the C-terminal domain of the RNA polymerase, and how a new phosphatase enzyme generates the form of the CTD found at the 3'-end of genes;(2) the molecular basis for RNA recognition by RNA processing factors in yeast and in vertebrates;(3) the interaction of RNA processing factors with factors that regulate RNA export.
Processing of the 3'-end of RNA by cleavage and polyadenylation is an essential maturation step that is increasingly understood to be critically regulated in cancer and development. Studying structurally and molecularly how it occurs, as we propose, is essential to understanding gene expression and its regulation.
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