3D STRUCTURE OF THE HUMAN RISC-LOADING COMPLEX

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 RNA干扰(RNAi)是一种广泛存在的真核基因沉默机制，在人类生物学的许多方面发挥着基础性的作用，包括发育计时、干细胞分裂、记忆和学习。在分子水平上，RNAi是由一系列被称为RNA诱导沉默复合体(RISC)的核糖核蛋白复合体介导的，它通过介导靶向信息RNA(MRNA)的翻译抑制和降解来沉默基因。RNAi的多功能性和强大功能源于这样一个事实，即RISC可以被编程为靶向任何核酸序列以进行沉默。因此，RISC编程是一项关键的细胞功能，需要一种名为RISC负载复合体(RLC)的特殊大分子组装的作用。这项提议的目标是确定人类RLC的3D架构。这些信息将为RNAi的启动提供机械性的见解，并可能为基于RNAi的治疗的发展提出新的策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. RNA interference (RNAi) is a broad-spread eukaryotic mechanism of gene silencing that plays a fundamental role in many aspects of human biology, including developmental timing, stem cell division, memory and learning. On the molecular level RNAi is mediated by a family of ribonucleo-protein complexes called RNA-Induced Silencing Complexes (RISC), which silence genes by mediating translational repression and degradation of targeted message RNAs (mRNA). The versatility and power of RNAi arises from the fact that RISC can be programmed to target any nucleic acid sequence for silencing. RISC programming is therefore a critical cellular function, requiring the action of a specialized macromolecular assembly called the RISC-loading complex (RLC). The goal of this proposal is to determine the 3D architecture of the human RLC. This information will offer mechanistic insight into the initiation of RNAi and may suggest novel strategies for the development of RNAi-based therapeutics.