杂合G-四链体的结构形成机制及其对转录的调控分子机理

项目名称： 杂合G-四链体的结构形成机制及其对转录的调控分子机理

项目编号： No.31470783

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 谭铮

作者单位： 中国科学院动物研究所

项目金额： 85万元

中文摘要： 富G核酸能够折叠，通过鸟嘌呤间的Hoogsteen氢键形成G-quadruplex（G-四链体）结构。G-四链体在癌基因启动子区富集，表明G-四链体有基因表达调控方面的功能，是基因表达的重要调控元件。近年来的研究发现能够形成G-四链体的序列在人的基因组中有几十万之多，G-四链体在活细胞基因组中的存在刚刚被证实。目前有关G-四链体的研究大多采用G-四链体核心序列，在静态的体外环境中进行。本实验室率先进行了生理动态过程G-四链体结构的形成，发现DNA转录诱导产生DNA:RNA杂合G-四链体并且其形成位点集中于转录起始位点且其数量与基因转录组表达具有对应关系，表明DNA本身编码有以杂合G-四链体结构形式的控制原件。本项目将继续研究基因组DNA中G-四链体结构的形成机制，结构转换动力学以及对转录调控的分子机制；同时探讨通过杂合G-四链体调控基因转录组表达的途径。

中文关键词： G-四链体；核酸结构；转录调控

英文摘要： Guanine-rich nucleic acids can fold into a four-stranded structure called G-quadruplex. Putative G-quadruplex sequences are enriched in the promoter regions of oncogenes. This fact implies that G-quadruplexes may function as regulatory elements and play role in the regulation of gene function. Recent research revealed hundreds and thousands of potential G-quadruplex sequences in the genome of human and other species. The existence of G-quadruplex structure has just been verified. So far, researches on G-quadruplex have been mostly carried out using core G-quadruplex sequences in a static and physiologically irrelevant environment. How G-quadruplexes are formed under the in vivo cellular condition; how the structure formation is affected or regulated by environmental factors; and what basic functions and biological effect G-quadruplex may have; all these questions needs to be addresses systematically. This proposal is aimed to elucidate the mechanism of structural formation, competition and regulation on transcription in physiologically relevant processes, such as replication, transcription and repair. We will also explore the possibility of altering gene expression by interrupting G-quadruplex formation.

英文关键词： G-quadruplex;Nucleic Acids;transcription regulation