TLS蛋白参与调控正性转录延伸因子b乙酰化/去乙酰化修饰的作用及机制

项目名称： TLS蛋白参与调控正性转录延伸因子b乙酰化/去乙酰化修饰的作用及机制

项目编号： No.31200981

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 杜昆

作者单位： 深圳大学

项目金额： 25万元

中文摘要： 正性转录延伸因子b是真核细胞基因转录过程中延伸阶段的关键调控蛋白,其正常功能依赖于它失活/活化两种形式的动态平衡。7SK-RNA和HEXIM1参与调控这个平衡。研究表明正性转录延伸因子b的乙酰化/去乙酰化修饰在此调控中起重要作用，但具体机制仍需探讨。根据已有文献和初步试验结果我们推测，在7SK-RNA的协助下TLS通过抑制HEXIM1/乙酰化酶/去乙酰化酶复合体的乙酰化酶活性参与调控正性转录延伸因子b的乙酰化修饰状态。为证实上述推测，本项目拟阐明如下四个问题⑴7SK-RNA协助TLS和HEXIM1结合⑵TLS及TLS/7SK-RNA对HEXIM1和乙酰化酶或去乙酰化酶结合的影响及机制⑶TLS及TLS/7SK-RNA对HEXIM1复合体乙酰化酶活性的影响⑷TLS对正性转录延伸因子b乙酰化状态的影响。本项目是对基因转录调控中一个细节机制的探索，有助于更好地了解上述各分子所参与的生理病理过程。

中文关键词： EP300；GAS5；TLS；膀胱癌；前列腺癌

英文摘要： RNA polymerase Ⅱ-dependent transcription can be subdivided into multiple stages, of which elongation stage is considered to be the major rate-limiting step. P-TEFb, positive transcriptional elongation factor b, as the name suggested, plays a key role in the transition of abortive elongation to productive elongation. Cellular P-TEFb presents in two distinct forms, the active and inactive form. The normal function of P-TEFb depends on the dynamic equilibrium of the two forms. Cooperating with HEXIM1, 7SK-RNA takes part in regulating the equilibrium of p-TEFb. Evidence shows that the acetylation/deacetylation of P-TEFb plays an important role in the equilibrium, but the mechanism remains largely unknown. We screened the RNAs that bind to TLS, a RNA binding protein with transcriptional acitvity, and identified the 7SK-RNA as a new partner of TLS. Our prelimilary results and other's published data suport the idea that TLS, facilitated by 7SK-RNA, modulates the acetyltransferase/deacetyltransferase activities of HEXIM1 complex,and consequently affects the acetylation/deacetylation of P-TEFb. The current proposal is aimed to testify the above idea by focucing on the following four poits. Firstly, the role amd mechanism of 7SK-RNA on facilitating the interaction of TLS and HEXIM1. Secondly, the effect of TLS or TLS/

英文关键词： EP300；GAS5；TLS；Bladder cancer；prostate cancer