The long-term goal of this study is to understand the biochemical mechanisms that underlie the regulation of eukaryotic mRNA synthesis. Specifically, the studies focus on understanding how the activity of the mammalian RNA polymerase II is controlled by transcription factors that direct initiation and elongation of transcripts from a large number of core promoters in vitro. The overall approach is to reconstitute with purified enzymes, faithful and efficient transcription in vitro, and to use this reconstituted system to elucidate the biochemical mechanisms governing transcription initiation and elongation by mammalian RNA polymerase II. The research will be organized along the following lines: (1) Detailed analysis of the mechanisms of action of novel RNA polymerase II elongation factors ELL and ELL2. (2) Further investigation of the mechanism of action of RNA polymerase II elongation factor Elongin. (3) Purification and characterization of RNA polymerase II elongation factor S-IV. (4) Detailed Investigation of the roles of TFIIE, TFIIF, TFIIH and ATP in transcription initiation and efficient promoter escape by RNA polymerase II. Additionally, studies are proposed to continue the studies on the functional relationship between the Elongin B and C regulatory subunits and the product of the VHL tumor suppressor gene.
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