RNA编辑对布氏锥虫线粒体基因表达的调控作用及分子机理研究

项目名称： RNA编辑对布氏锥虫线粒体基因表达的调控作用及分子机理研究

项目编号： No.31200952

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： 张小白

作者单位： 同济大学

项目金额： 25万元

中文摘要： 布氏锥虫（T. brucei）是一种对人类和家畜有严重危害的寄生原虫，同时也是一种重要的模式生物。T. brucei的整个生命周期伴随着线粒体生物发生（biogeneis）的调控，但调控机制不清楚。我们前期研究发现T. brucei中核基因编码的线粒体蛋白质受到反式剪接的显著调控作用。本项目将通过转录组测序与生物信息分析，研究RNA编辑对T. brucei线粒体基因表达的调控作用及分子机理。针对锥虫线粒体中RNA编辑的特点，本研究将建立一套锥虫线粒体转录组分析方法，研究不同生命周期阶段T. brucei线粒体基因的差异表达情况，分析各种可变编辑模式及其对基因编码产物的影响，识别可变编辑所需的特异gRNA（guide RNA），并阐释RNA编辑与反式剪接对线粒体生物发生的协同调控作用。本研究将有助于加深对T. brucei线粒体生物发生调控机制的认识，为锥虫病治疗药物的研发提供重要线索。

中文关键词： 布氏锥虫；RNA编辑；基因表达调控；线粒体生物发生；鞭毛蛋白

英文摘要： Trypanosoma brucei (T. brucei) is a unicellular protozoan parasite greatly harmful to both human and livestock. Besides, it has also proved to be a valuable model organism. Its mitochondrial biogenesis is developmentally regulated during its life cycle, but the regulation mechanism remains unclear. Our previous work showed that the expression of nucleus-encoded mitochondrial proteins is significantly regulated by trans-splicing. In this proposal, we plan to use RNA-seq technology and bioinformatics approaches to study the functional roles of RNA editing in mitochondrial gene expression regulation in T. brucei. Based on the characterization of RNA editing in T. brucei, special mitochondrial transcriptome analysis pipeline will be established to systematically analyze the expression profiles of T. brucei mitochondrial genes in different life cycle stages. The study aims to identify differentially expressed genes, distinguish alternative RNA editing patterns and investigate the potential roles of the corresponding products. In order to reveal the molecular mechanism of alternative RNA editing, a prediction tool will be developed to recognize the specific gRNAs (guide RNA) responsible for RNA editing. Furthermore, we will investigate the collaborative regulation of RNA editing and trans-splicing to mitochondrial bio

英文关键词： Trypanosoma brucei；RNA editing；gene expression regulation；mitochondrial biogenesis；flagellar protein