BIOCHEMISTRY OF EUKARYOTIC MESSENGER RNA SYNTHESIS

超出所提供的空间。这项研究的长期目标是有助于了解真核生物信使RNA合成调控的生化机制。在整个过程中，这个补助金，我们一直试图确定，在分子水平上，哺乳动物RNA聚合酶II的活性是如何控制的一般启动因子和一组延伸因子的作用，共同发挥作用，以指导准确的启动和有效的延伸。这项工作导致RNA聚合酶II的一般起始因子和延伸因子Elongin和ELL的纯化和表征。我们对RNA聚合酶II延伸因子Elongin的研究为研究von HippeI-Lindau（VHL）肿瘤抑制蛋白的作用机制开辟了一条新的生产线。这项工作导致发现VHL蛋白是基于Elongin BC的E3泛素连接酶的新家族的组成部分。在延长MERIT奖期间，我们计划扩展我们对RNA聚合酶II转录的机制和调节以及VHL肿瘤抑制蛋白作用机制的研究，如下所述。总体目标与上一次竞争性更新相同：（1）在延伸过程中控制哺乳动物RNA聚合酶II活性的转录因子的纯化和分析。(2)RNA聚合酶II启动子特异性转录的生化机制分析。(3)研究VHL泛素连接酶复合物和相关的基于Elongin BC的泛素连接酶家族成员的作用机制。性能现场=

EXCEED THE SPACE PROVIDED. The long range goal of this research is to contribute to an understanding of the biochemical mechanisms underlying the regulation of eukaryotic messenger RNA synthesis. Throughout the course of this grant, we have sought to determine, at the molecular level, how the activity of mammalian RNA polymerase II is controlled by the action of the general initiation factors and a set of elongation factors that function together to direct accurate initiation and efficient elongation. This work led to the purification and characterization of the RNA polymerase II general initiation factors and elongation factors Elongin and ELL. Our studies of RNA polymerase II elongation factor Elongin opened up a new and productive line of research on the mechanism of action of the von HippeI-Lindau (VHL) tumor suppressor protein. This work led to the discovery that the VHL protein is an integral component of a new family of Elongin BC-based E3 ubiquitin ligases. During the extension of this MERIT Award, we plan to extend our studies of the mechanism and regulation of RNA polymerase II transcription and of the mechanism of action the VHL tumor suppressor protein as outlined below. The overall aims remain the same as in the last competing renewal: (1) Purification and analysis of transcription factors that control the activity of mammalian RNA polymerase II during elongation. (2) Analysis of the biochemical mechanism of promoter-specific transcription by RNA polymerase II. (3) Investigation of the mechanisms of action of the VHL ubiquitin ligase complex and of members of the family of related Elongin BC-based ubiquitin ligases. PERFORMANCE SITE ========================================Section End===========================================