It is becoming increasingly clear that in mammalian cells, RNA Polymerase II is regulated at the level of promoter proximal pause release and productive elongation prompted by P-TEFb kinase activity. As a result, P-TEFb recruitment and activation at particular gene promoters is a key regulatory switch, the understanding of which can open the way to new therapeutic opportunities for many diseases including cancer. P-TEFb activity is inhibited by its interaction with the 7SK ribonuclear protein complex (RNPc), which sequesters unutilized P-TEFb in the nucleoplasm; interestingly, recent studies, including ours, have shown that this RNPc often regulates P-TEFb recruitment and activity directly on chromatin at the promoter of paused genes. Here, we will present our data showing how MePCE, an RNA methyltransferase of the 7SK RNPc, multitasks on chromatin to coordinate transcription and RNA processing with other DNA-templated activities, including DNA repair.
Support or Funding Information
National Institutes of Health, GM127802; Department of Defense Breast Cancer Research Program, Breakthrough Award, BC151608; CPRIT RP120348 and RP170002; University of Texas at Austin start up funds.
National Institutes of Health, GM127802; Department of Defense Breast Cancer Research Program, Breakthrough Award, BC151608; CPRIT RP120348 and RP170002; University of Texas at Austin start up funds.