Molecular analysis of transcription termination by human RNA polymerase II

描述(申请人提供)：RNA聚合酶II终止的分子机制仍然知之甚少。信使核糖核酸3‘末端的处理与终止有关，而这一处理步骤的解除调控会导致人类疾病。该项目的长期目标是表征共转录加工因子在RNA3‘末端加工和PolII转录终止中的作用。本研究的目的是：1：确定哺乳动物PolII依赖PolyA位点终止的相关因素；2：研究延长因子Spt5在POLII 3‘末端加工和终止中的作用。我们将进行全基因组RNAi筛选，以确定在人类细胞中终止PolII所需的新因素。该检测的变异可能进一步用于确定某些癌症中观察到的替代Poly(A)位点选择所涉及的因素。

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.