RNA Mediated Genetic Interference in C. elegans

描述（由申请人提供）：这里描述的研究旨在理解被称为RNAi的基因沉默现象。在RNAi过程中，dsRNA指导转录后序列特异性抑制基因表达。最近的研究已经开始揭示dsRNA如何转化为一种有效的基因沉默剂，以及相关机制在多种动物和植物的种系维持和发育基因调控中的重要作用。拟议的研究将采用一套完整的分子、生化和遗传方法，以秀丽隐杆线虫为模型系统，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和相关途径中起作用？这些研究的发现将促进我们对包括人类在内的其他生物中RNAi和相关途径的理解，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有关，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性的新见解。

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.