EUBACTERIAL ARGONAUTE COMPLEXES BOUND TO GUIDE DNA AND TARGET RNA

真细菌 Argonaute 复合物结合引导 DNA 和目标 RNA

• 批准号: 7955161
• 负责人: DINSHAW J PATEL
• 金额: $ 0.73万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955161
• 关键词: Address; Binding; Complex; Computer Retrieval of Information on Scientific Projects Database; DNA; Disease; Funding; Gene Silencing; Goals; Grant; Individual; Institution; Lead; Mediating; Messenger RNA; Molecular; Nucleic Acids; Play; Proteins; RNA; RNA Interference; RNA Interference Pathway; RNA-Induced Silencing Complex; Research; Research Personnel; Resources; Role; Small Interfering RNA; Source; Structure; Techniques; Technology; Therapeutic; United States National Institutes of Health; base; nuclease; scaffold; structural biology

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 techniques have revolutionized our ability to silence genes and hold great promise as a therapeutic approach against a diverse set of diseases. To use this technology optimally, one needs to decipher the molecular basis underlying individual steps in the catalytic cycle that eventually lead to degradation of the targeted message. This project focuses on one critical component of the degradation machinery, the Argonaute (Ago) protein, and addresses its ability to accommodate a nucleic acid template (guide strand) within its scaffold, and defines key features of its alignment for pairing and subsequent nuclease-mediated cleavage of the message. The Ago protein, composed of PAZ- and PIWI-containing modules, as a key catalytic component of the RNA-induced silencing complex (RISC), plays a central role in the RNA interference pathway by mediating sequence-specific cleavage of target messenger RNA (mRNA), including the maturation of small interfering RNA (siRNA) through initial degradation of the passenger strand. Our goal is to determine structures of Ago-nucleic acid complexes during distinct assembly and functional steps of the RNA interference catalytic cycle in order to define the mechanisms underlying guide strand mediated targeting and degradation of mRNA.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 RNA 干扰技术彻底改变了我们沉默基因的能力，并有望作为多种疾病的治疗方法。为了最佳地使用这项技术，人们需要破译催化循环中各个步骤的分子基础，这些步骤最终导致目标信息的降解。该项目重点关注降解机制的一个关键组成部分——Argonaute (Ago) 蛋白，并解决其在其支架内容纳核酸模板（引导链）的能力，并定义其配对和随后核酸酶介导的信息切割的对齐的关键特征。 Ago 蛋白由包含 PAZ 和 PIWI 的模块组成，作为 RNA 诱导沉默复合物 (RISC) 的关键催化成分，通过介导目标信使 RNA (mRNA) 的序列特异性切割，包括通过过客链的初始降解来成熟小干扰 RNA (siRNA)，在 RNA 干扰途径中发挥核心作用。 我们的目标是在 RNA 干扰催化循环的不同组装和功能步骤中确定 Ago-核酸复合物的结构，以便定义引导链介导的 mRNA 靶向和降解的机制。