DISTINCT ARGONAUTE-MEDIATED 22G-RNA PATHWAYS DIRECT GENOME SURVEILLANCE

独特的 Argonaute 介导的 22G-RNA 通路直接基因组监测

• 批准号: 8171280
• 负责人: CRAIG C MELLO
• 金额: $ 0.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171280
• 关键词: Alleles; Biogenesis; Biological Process; Caenorhabditis elegans; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytoplasmic Granules; Funding; Genes; Genetic; Genome; Grant; Institution; Mediating; Nonsense-Mediated Decay; Pathway interactions; Proteins; Pseudogenes; RNA Interference; RNA-Directed RNA Polymerase; Regulation; Research; Research Personnel; Resources; Small RNA; Source; Structure; System; United States National Institutes of Health; helicase; human DICER1 protein

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. Endogenous small RNAs (endo-siRNAs) interact with Argonaute (AGO) proteins to mediate sequence-specific regulation of diverse biological processes. Here, we combine deep-sequencing and genetic approaches to explore the biogenesis and function of endo-siRNAs in C. elegans. We describe conditional alleles of the Dicer-related helicase, drh-3, that abrogate both RNA interference and the biogenesis of endo-siRNAs, called 22G-RNAs. DRH-3 is a core component of RNA-dependent RNA polymerase (RdRP) complexes essential for several distinct 22G-RNA systems. We show that, in the germline, one system is dependent on worm-specific AGOs, including WAGO-1, which localizes to germline nuage structures called P granules. WAGO-1 silences certain genes, transposons, pseudogenes, and cryptic loci. Finally, we demonstrate that components of the nonsense-mediated decay pathway function in at least one WAGO-mediated surveillance pathway. These findings broaden our understanding of the biogenesis and diversity of 22G-RNAs and suggest additional regulatory functions for small RNAs.

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。 内源性小 RNA (endo-siRNA) 与 Argonaute (AGO) 蛋白相互作用，介导多种生物过程的序列特异性调节。在这里，我们结合深度测序和遗传学方法来探索秀丽隐杆线虫中内切 siRNA 的生物发生和功能。我们描述了 Dicer 相关解旋酶 drh-3 的条件等位基因，它消除了 RNA 干扰和内切 siRNA（称为 22G-RNA）的生物发生。 DRH-3 是 RNA 依赖性 RNA 聚合酶 (RdRP) 复合物的核心成分，对于几种不同的 22G-RNA 系统至关重要。我们表明，在种系中，一个系统依赖于蠕虫特异性 AGO，包括定位于种系的 WAGO-1 称为 P 颗粒的微小结构。 WAGO-1 沉默某些基因、转座子、假基因和隐性基因座。最后，我们证明无义介导的衰变途径的组成部分在至少一种 WAGO 介导的监视途径中发挥作用。这些发现拓宽了我们对 22G-RNA 生物发生和多样性的理解，并提示小 RNA 具有额外的调节功能。