Molecular analysis of transcription termination by human RNA polymerase II

描述（由申请人提供）：RNA聚合酶II终止的分子机制仍然知之甚少。mRNA 3'端加工与终止相耦合，这一加工步骤的解除导致人类疾病。该项目的长期目标是表征共转录加工因子在RNA 3'端加工和pol II转录终止中的作用。本提案的目的是：1：确定哺乳动物poly(A)位点依赖性pol II终止的相关因素，2：研究延伸因子Spt5在pol II 3'端加工和终止中的作用。我们将进行全基因组范围的RNAi筛选，以确定人类细胞中pol II终止所需的新因子。该试验的变化可能进一步用于确定在某些癌症中观察到的选择性多聚(A)位点选择的因素。

DESCRIPTION (provided by applicant): The molecular mechanisms of RNA polymerase II termination remain poorly understood. mRNA 3' end processing is coupled to termination, and deregulation of this processing step results in human disease. The long-term objective of this project is to characterize the role of co-transcriptional processing factors in RNA 3' end processing and pol II transcriptional termination. The aims of this proposal are 1: to determine factors involved in mammalian poly(A) site dependent pol II termination, and 2: to investigate the role of the elongation factor Spt5 on pol II 3' end processing and termination. We will conduct a genome wide RNAi screen designed to identify new factors required for pol II termination in human cells. Variations on this assay might further be used to identify factors involved in alternative poly(A) site choice observed in certain cancers. PUBLIC HEALTH RELEVANCE: There are a growing number of human diseases, including cancer, that are characterized by incorrect or alternate 3' end formation of gene transcripts. mRNA 3' end processing is coupled to RNA polymerase termination. With this project I hope to determine the molecular mechanisms of transcriptional termination, and thereby expand upon our understanding of these diseases.