ABC Transporters and RNAi in Caenorhabditis Elegans

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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.