RNA Mediated Genetic Interference in C. elegans

描述(由申请人提供)：这里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指导转录后序列特异性的基因表达抑制。最近的研究已经开始揭示dsRNA是如何转化为一种有效的基因沉默因子，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套综合的分子、生化和遗传学方法，以线虫秀丽线虫为模式系统，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；信使核糖核酸的破坏与翻译抑制？以及(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RNAi和包括人类在内的其他生物中相关途径的理解，并可能导致改进遗传干扰技术。此外，由于RNAi的遗传机制与古老的基因调控机制有关，拟议的研究将带来对我们理解人类发育和疾病具有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.