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理解真核信使RNA合成调控的生化机制。在整个资助过程中，我们试图确定，在分子水平上，哺乳动物RNA聚合酶II的活性是如何由一般起始因子和一组延伸因子的作用控制的，这些因子共同起作用，指导精确的起始和有效的延伸。这项工作导致RNA聚合酶II一般起始因子和延伸因子伸长和ELL的纯化和表征。我们对RNA聚合酶II延伸因子伸长素的研究，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研究思路。这项工作导致发现VHL蛋白是一个基于长链蛋白bc的E3泛素连接酶新家族的组成部分。在此MERIT奖的扩展期间，我们计划扩展我们对RNA聚合酶II转录的机制和调控以及VHL肿瘤抑制蛋白的作用机制的研究，如下所述。总体目标与上次竞争更新相同：(1)纯化和分析在伸长过程中控制哺乳动物RNA聚合酶II活性的转录因子。(2) RNA聚合酶启动子特异性转录的生化机制分析。(3) VHL泛素连接酶复合物及相关的基于长链蛋白bc的泛素连接酶家族成员的作用机制研究。网站性能 ======================================== 节结束 ===========================================

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===========================================