RNA诱导沉默复合体的装配及其在RNAi中的作用(论文资料).docVIP

RNA诱导沉默复合体的装配及其在RNAi中的作用 摘要：RNA诱导沉默复合体( RNA-induced silencing complex，RISC) 是RNA 干扰( RNA interference, RNAi)过程中的重要活性成分,它由Dicer 酶, Argonaute蛋白, siRNA 等多种生物大分子装配而成。在RNA 干扰机制中, 双链RNA 诱导同源RNA 降解的过程依赖于RNA 诱导沉默复合体( RISC) 的活性，而RISC的装配受到TRBP的调节。因此，对这些大分子的结构和功能进行深入细致的研究, 有助于进一步了解RISC 的形成过程、作用方式, 以及阐明整个RNAi 过程的作用机制。研究表明, RISC 中的Dicer 具有RNaseIII 结构域, 在RNAi 的起始阶段负责催化siRNA 的产生, 在RISC 装配过程中起稳定RISC 中间体结构和功能的作用; Argonaute 蛋白是RISC 中的核心蛋白, 有PAZ 和PIWI 两个主要的结构域, 前者为siRNA 的传递提供结合位点, 后者是RISC 中的酶切割活性中心; siRNA是RISC 完成特异性切割作用的向导, 在成熟的RISC中虽然只包含siRNA的一条链, 但siRNA 在RISC 形成过程中的双链结构是保证RNAi 效应的决定因素。随着对RNAi 机制研究的日益深入,人们对RISC组分的结构、功能进行了较详细的研究并取得一定进展, 这不但有助于了解RISC 的形成过程、作用方式, 也有利于进一步阐明整个RNAi 作用的机制。 关键词：RNA干扰；RNA诱导沉默复合体；装配 RNA-induced Silencing Complex Assembly and Its Functions in RNA Interference ZHANG rui-quan (Biological science base class ,School of Life Science，20101070109) Abstract: RNA-induced silencing complex is the active ingredient in the process of RNA interference, assembled by Dicer, Argonaute, siRNA, and other biological macromolecules. Degradation of homologous RNA in RNA interference is carried out by functional RNA-induced silencing complex(RISC), and RISC assembly regulation by TRBP. So Researching structures and functions of these components is primary impor tant for understanding assembly and functional mechanism of RISC, as well as the whole RNAi pathway. Recent research works showed that Dicer, containing RNaseIII domain, is responsible for production of siRNA at the beginning of RNAi, and guarantees the stability of RISC intermediate in assembly process. As the core component of RISC, Argonaute protein functions as slicer to cleave target RNA and offers the binding site of siRNA in RISC assembly, which are depended on PIWI domain and PAZ domain separately. Although there is only one strand of siRNA that is the guider of RISC, the double stranded structural character of siRNA is determinant of RNAi. With the deepening of the RNAi mechanism on the the RISC components o