| RNA interference (RNAi) is a recently discovered phenomenon in which double-stranded RNA (dsRNA) silences endogenous gene expression in a sequence-specific manner. RNAi shares a remarkable degree of similarity with silencing phenomena in other organisms, suggesting that RNAi is part of an ancient and conserved pathway used to regulate gene expression, to eliminate defective RNAs and to defend against viral infections and transposons. RNAi has also been implicated in developmental processes, suggesting that RNAi may play a broader role in regulating normal gene expression. Since its discovery, the use of RNAi has become widely employed in many organisms to specifically knock down gene function. Although we have learned much about the general mechanisms underlying RNAi, a detailed understanding of how RNAi works remains to be elucidated.;I have developed a candidate screen approach in which I use RNAi to identify genes required for RNAi. I identified a number of potential candidates and in a secondary screen, using mutant animals, validated roles for several new genes in RNAi. Interestingly, many of these genes encode protein known to function in the nucleus, and some of the genes identified are members of the well characterized SynMuv B pathway. In addition, I have further characterized the role of a nuclear RNA helicase. These results suggest clues and provide important tools toward furthering our emerging understanding of nuclear mechanisms of RNAi interference in animals. |
