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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 内源性小RNA（endo-siRNA）与Argonaute（AGO）蛋白相互作用以介导多种生物过程的序列特异性调节。在这里，我们结合联合收割机深度测序和遗传学方法来探索C.优美的我们描述了Dicer相关解旋酶drh-3的条件等位基因，该等位基因消除了RNA干扰和称为22 G-RNA的内切siRNA的生物发生。DRH-3是RNA依赖性RNA聚合酶（RdRP）复合物的核心组分，对于几种不同的22 G-RNA系统是必需的。我们发现，在种系中，一个系统依赖于蠕虫特异性AGO，包括WAGO-1，其定位于种系 称为P颗粒的纳米结构。WAGO-1使某些基因、转座子、假基因和隐蔽基因座沉默。最后，我们证明了无义介导的衰变途径的组件在至少一个WAGO介导的监视途径中发挥作用。这些发现拓宽了我们对22 G-RNA的生物起源和多样性的理解，并表明小RNA具有额外的调控功能。