Regulation of the RNA interference pathway in Drosophila

RNA silencing has enormous biotechnological and therapeutic potential. Drosophila has proved to be the best model for understanding RNA silencing in humans. In flies, two classes of small non-coding RNAs-microRNAs (miRNAs) and small interfering RNAs (siRNAs)-act via conceptually similar but distinct mechanisms. Although key protein components-each of which has a closely related human counterpart-have been identified for these two Drosophila RNA silencing pathways, we do not understand how these pathways are regulated in vivo. Published and unpublished data suggest that the siRNA-directed RNA interference (RNAi) pathway is repressed in some tissues and induced by exposure to double-stranded RNA (dsRNA) in others, suggesting that the activity of the RNAi pathway is regulated in vivo. Using a combination of genetics and biochemistry, I will seek to explain how the RNAi pathway is repressed in the Drosophila germ line and to determine if the RNAi pathway is activated upon exposure to double-stranded RNA, much as other innate immune pathways are up-regulated by their triggers.