细胞骨架细丝蛋白A在RNA聚合酶III指导的基因转录中的作用机制研究

项目名称： 细胞骨架细丝蛋白A在RNA聚合酶III指导的基因转录中的作用机制研究

项目编号： No.31271395

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 邓文生

作者单位： 武汉科技大学

项目金额： 80万元

中文摘要： 细丝蛋白A（FLNA）在细胞中起着多种作用，我们前期的研究表明FLNA位于细胞的核仁区，并抑制核糖体RNA基因转录和细胞增殖。由于核糖体RNA（28S，18S，5.8S rRNA）由RNA聚合酶I转录，而核糖体5S rRNA由RNA聚合酶III转录，由此假设：FLNA也能调节RNA聚合酶III(pol III)指导的转录。我们最近的研究结果表明FLNA siRNA 能增强5S rRNA 和2个tRNA 基因的表达；荧光染色和免疫沉淀证明FLNA能与转录因子TFIIIC2结合。本项目将继续研究FLNA在RNA聚合酶III指导的转录中的作用及其机制，包括：1.FLNA调节哪些pol III控制的基因？2.FLNA是否直接参与此过程的调节？3.FLNA是否结合pol III 转录装置？4.FLNA如何调节pol III指导的转录机制。本研究将阐明FLNA在转录和细胞增殖中作用机制。

中文关键词： 转录；RNA 聚合酶 III；细丝蛋白 A；转移RNA；转化细胞系

英文摘要： Cytoskeletal protein filamin A(FLNA) plays diverse roles in human cell including cell adhension and migration,cell signalling, transcription and cytoskeleton maintenance. Our previous work showed that FLNA is localised to nucleolus and represses ribosomal RNA（rRNA） gene transcription and cell proliferation. Since rRNAs including 28S,18S and 5.8S rRNA are important components of ribosome and transcribed by RNA polymerase I(pol I); whereas 5S rRNA, another component of ribosome, is transcribed by RNA polymerase III(pol III). It raises a hypothesis that FLNA could also regulate gene transcripion by RNA pol III. Indeed, our latest data show that FLNA siRNA is able to stimulate 5S rRNA and two tRNA genes expression in Saos2 cell. Using immunofluorescence staining immunoprecipitation methods we demonstrated that FLNA associates with transcription factor TFIIIC2. Together, these data indicate that FLNA is invovled in the regulation of gene trnscription by RNA polymerase III. In this project we'll further investigate the role of FLNA and its regulatory mechanism in gene transcription by RNA pol III through performing the following work：1）determine what pol III-controlled genes are modulated by FLNA. 2) determine whether filamin A directly involves pol III-directed transcription. 3)understand whether FLNA binds RNA p

英文关键词： transcription；RNA polymerase III；filamin A；tRNA；transformed cell lines