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

使用比较遗传学和基因组学剖析线虫和布里格斯线虫的小 RNA 通路

• 批准号: 418683-2012
• 负责人: Claycomb, Julie
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629837
• 关键词: Dissecting; small; RNA; pathways; using

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.

RNA干扰（RNAi）是一种细胞过程，其中特定基因的表达通过由小RNA分子与Argonaute蛋白作用组成的酶复合物的作用而沉默。这些小RNA分子为Argonaute提供序列特异性基因靶向活性，Argonaute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，它已经成为一种几乎无处不在的实验室工具，彻底改变了一些以前在遗传学上难以解决的研究系统。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，从而阻止肿瘤发生。与RNAi密切相关的其他细胞机制在各种生物体中是保守的，从植物到蠕虫和人类。这种内源性基因沉默途径在正常过程如细胞分化、发育和配子形成期间调节基因表达中起关键作用。因此，对内源性沉默的研究将揭示对各种生物体中有助于发育和分化的基本细胞功能的更深入理解。小线虫C.线虫已被证明是理解RNAi和内源性小RNA途径的分子机制的理想模型。因此，我们将使用C。elegans和一种叫做C. briggsae的研究，以更好地了解小RNA介导的基因调控机制的进化差异，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。