Dissecting small RNA pathways using comparative genetics and genomics in C. elegans and C. briggsae

RNA干扰(RNAi)是一种细胞过程，在这种过程中，特定基因的表达被由小RNA分子与ArgAerte蛋白作用组成的酶复合体的作用所沉默。这些小的RNA分子为Argavite提供序列特异性的基因靶向活性，这是沉默的催化剂。在过去的十年里，RNAi一直是人们非常感兴趣的话题，在此期间，它已经成为一个几乎无处不在的实验室工具，彻底改变了一些研究系统中以前在遗传上难以处理的研究。RNAi还具有巨大的治疗潜力；想象一下，能够随意关闭导致癌症进展的特定基因，从而阻止肿瘤生成。 其他与RNAi密切相关的细胞机制在各种生物中都是保守的，从植物到蠕虫和人类。这些内源性基因沉默途径在细胞分化、发育和配子形成等正常过程中调节基因表达起着关键作用。因此，对内源性沉默的研究将有助于更深入地了解促进各种生物体发育和分化的基本细胞功能。 微小线虫线虫已被证明是理解RNAi和内源小RNA途径的分子机制的理想模型。因此，我们将以线虫和一种独特的线虫物种为例，更好地了解小RNA介导的基因调控机制中的进化差异，并增加我们对这些关键基因沉默途径的分子机制的整体知识。

RNA interference (RNAi) is a cellular process whereby the expression of a specific gene is silenced by the action of an enzymatic complex composed of a small RNA molecule acting with an Argonaute protein. These small RNA molecules provide sequence-specific gene targeting activity to the Argonaute, which is the catalyst of silencing. RNAi has been the topic of much interest over the past decade, during which time it has become a nearly ubiquitous laboratory tool, revolutionizing studies in some research systems that were previously genetically intractable. RNAi also holds great therapeutic potential; imagine being able to turn off a specific gene that contributed to cancer progression at will, thus halting oncogenesis. Other cellular mechanisms closely related to RNAi are conserved in various organisms, from plants to worms and humans. Such endogenous gene silencing pathways play key roles in regulating gene expression during normal processes such as cell differentiation, development, and gamete formation. Thus, studies of endogenous silencing will reveal a deeper understanding of the basic cellular functions that contribute to development and differentiation in various organisms. The tiny nematode C. elegans has proven an ideal model for understanding the molecular mechanisms of RNAi and endogenous small RNA pathways. Accordingly, we will use C. elegans and a distinct nematode species called C. briggsae to better understand the evolutionary differences in small RNA-mediated gene regulatory mechanisms, and to increase our overall knowledge of the molecular mechanisms of these critical gene silencing pathways.