ABC Transporters and RNAi in Caenorhabditis Elegans

RNA干扰(RNAi)技术利用特定的双链RNA序列来沉默特定基因的表达。术语RNAi还指一套广泛的保守机制，允许大多数生物体的细胞对双链RNA做出反应。这些机制在细胞中具有重要的内源性作用，包括影响染色质功能的作用。例如，RNAi机制有助于建立异染色质，这是防止转座子动员的重要功能。ABC转运蛋白是一种跨膜蛋白，起到泵的作用，通过膜双层运输小分子。许多ABC转运蛋白基因存在于大多数生物体中，它们共同具有与底物运输相关的不同功能。一些转运体通过出口有毒物质来缓解细胞压力，而另一些转运体则运输对正常健康和发育至关重要的特定底物。许多转运蛋白运输的底物及其在细胞中的确切功能尚未确定。在我们对线虫线虫RNAi缺陷株的分析过程中，我们观察到一些ABC转运蛋白基因是有效地对双链RNA做出RNAi反应以及影响染色质功能的内源RNAi活动所必需的。目前的项目将使我们能够确定ABC转运蛋白如何影响RNAi机制。我们的工作深入探索了一个新颖且尚未探索的领域，它将生物学中两个最保守的机制联系在一起。更广泛的影响：我们的研究目标的本质是允许本科生和研究生进行科学培训和职业发展的项目；学生还将参与旨在提高K-12水平科学素养的外展机会。

RNA interference (RNAi) technologies utilize a specific sequence of double-stranded RNA in order to silence the expression of a particular gene. The term RNAi also refers to a broad set of conserved mechanisms that allow cells from most organisms to respond to double-stranded RNA. These mechanisms have vital endogenous roles in cells, including roles that affect chromatin function. For example, RNAi mechanisms help establish heterochromatin, a function that is important in preventing mobilization of transposons. ABC transporters are transmembrane proteins that act as pumps to transport small molecules across a membrane bilayer. Many ABC transporter genes are found in most organisms, and they collectively harbor diverse functions associated with substrate trafficking. Some transporters alleviate cellular stress by exporting toxic substances, whereas other transporters traffic specific substrates that are vital to normal health and development. The substrates trafficked by many transporters, and their precise functions in cells, have yet to be identified. During the course of our analysis of RNAi-defective strains of the nematode worm Caenorhabditis elegans, we observed that some ABC transporter genes are required for an efficient RNAi response to double-stranded RNA as well as for endogenous RNAi activities that affect chromatin function. The current project will enable us to determine how ABC transporters influence RNAi mechanisms. Our work delves into a novel and as yet unexplored area that links two of the most conserved mechanisms in biology. Broader Impact: Intrinsic to our research goals are projects that will allow for scientific training and career development of undergraduate and graduate students; students will also be engaged in outreach opportunities directed toward enhancing scientific literacy at the K-12 level.