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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 RNA干扰技术彻底改变了我们沉默基因的能力，并具有对各种疾病的治疗方法，并保持了巨大的希望。为了最佳地使用这项技术，需要在催化周期中破译分子基础的基本步骤，从而最终导致目标消息的降解。该项目侧重于降解机械的一个关键组成部分，即Argona（AGO）蛋白质，并探讨了其在其支架内适应核酸模板（指导链）的能力，并定义了其对齐和随后的核酸酶介导的介导的消息的关键特征。由含PAZ和PIWI的模块组成的AGO蛋白是RNA诱导的沉默络合物（RISC）的关键催化成分，在RNA干扰途径中起着核心作用，通过介导靶Messenger RNA（mRNA）的序列序列特异性切割（MRNA），包括小型cressenter RNA（包括sirnna sirnna（sirnna）的成熟）（包括sirnna（mRNA）的成熟）。 我们的目标是确定在不同的组装和RNA干扰催化循环的功能步骤中确定AGO核酸复合物的结构，以定义MRNA的基础指南介导的靶向和降解的机制。