BIOCHEMISTRY OF EUKARYOTIC MESSENGER RNA SYNTHESIS

描述(改编自申请人的摘要)：该项目的长期目标 研究是为了了解这种调节的生化机制。 真核生物的信使核糖核酸合成。具体地说，这些研究侧重于理解 哺乳动物RNA聚合酶II的活性是如何由 指导转录本起始和延伸的转录因子 大量的核心启动子在体外。总体方法是 与纯化的酶重组，忠实而高效地转录在 并利用这个重组系统来阐明生物化学 哺乳动物RNA启动和延长转录的机制 聚合酶II.研究将按以下思路组织：(1) 新型RNA聚合酶II作用机制的详细分析 伸长系数EL1和ELL2。(2)进一步探讨心绞痛的作用机制 RNA聚合酶II延伸因子Elongin的作用。(3)净化和 核糖核酸聚合酶II延伸因子S-IV的特性。(4)详细说明 TFIIE、TFIIF、TFIIH和ATP在转录中的作用研究 通过RNA聚合酶II启动和有效的启动子逃逸。 建议继续对功能关系的研究 Elongin B和C调节亚基与VHL产物之间的关系 肿瘤抑制基因。

DESCRIPTION(adapted from applicant's abstract): 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.