RNA Mediated Genetic Interference in C. elegans

RNA 介导的线虫遗传干扰

• 批准号: 7037559
• 负责人: CRAIG C MELLO
• 金额: $ 31.05万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7037559
• 关键词: Caenorhabditis elegans; RNA interference; animal genetic material tag; artificial chromosomes; complementary RNA; double stranded RNA; enzyme activity; fusion gene; gene expression; gene induction /repression; genetic mapping; genetic regulation; genetic regulatory element; genetic screening; genetic strain; genetic transcription; helicase; in situ hybridization; messenger RNA; microinjections; natural gene amplification; nucleic acid metabolism; nucleic acid sequence; reporter genes; structural genes

DESCRIPTION (provided by applicant): The research described here is directed at understanding a gene-silencing phenomenon known as RNAi. During RNAi, dsRNA directs the post-transcriptional sequence-specific inhibition of gene expression. Recent studies have begun to reveal how dsRNA is converted into a potent gene-silencing agent, and how related mechanisms are important in germline maintenance and developmental gene regulation in a variety of animals and plants. The proposed studies will employ an integrated set of molecular, biochemical and genetic methods using the nematode Caenorhabditis elegans as a model system and will address the following questions; (i) How is RNAi initiated? (ii) How do RNAi and mechanistically related developmental pathways, direct distinct outcomes; mRNA destruction vs. translation inhibition? and (iii) what gene products function in RNAi and related pathways? The findings from these studies will advance our understanding of RNAi and of related pathways in other organisms including humans and may lead to improved genetic interference technologies. Moreover, because the genetic mechanisms of RNAi are related to ancient gene-regulatory mechanisms, the proposed studies will lead to new insights of potential importance to our understanding of human development and disease.

描述（由申请人提供）：此处描述的研究旨在了解一种称为 RNAi 的基因沉默现象。在 RNAi 过程中，dsRNA 指导基因表达的转录后序列特异性抑制。最近的研究已经开始揭示 dsRNA 如何转化为有效的基因沉默剂，以及相关机制如何在各种动植物的种系维持和发育基因调控中发挥重要作用。拟议的研究将采用一整套分子、生物化学和遗传学方法，使用线虫秀丽隐杆线虫作为模型系统，并将解决以下问题； (i) RNAi 是如何启动的？ (ii) RNAi 和机械相关的发育途径如何指导不同的结果； mRNA 破坏与翻译抑制？ (iii) 哪些基因产物在 RNAi 和相关途径中发挥作用？这些研究的结果将增进我们对 RNAi 以及包括人类在内的其他生物体相关途径的理解，并可能导致遗传干扰技术的改进。此外，由于RNAi的遗传机制与古老的基因调控机制相关，因此拟议的研究将为我们理解人类发育和疾病带来潜在重要的新见解。