Proteomics Identification of Drosophila Small Interfering RNA-associated Factors*□S

complex (RISC) forms a large ribonucleoprotein particle on small interfering RNAs (siRNAs) and catalyzes target mRNA cleavage during RNA interference (RNAi). Di-cer-2, R2D2, Loquacious, and Argonaute-2 are exam-ples of RISC-associated factors that are involved in RNAi. Holo-RISC is an 80 S small interfering ribonu-cleoprotein, which suggests that there are many addi-tional proteins that participate in the RNAi pathway. In this study, we used siRNA affinity capture combined with mass spectrometry to identify novel components of the Drosophila RNAi machinery. Our study identified both established RISC components and novel siRNA-associated factors, many of which contain domains that are consistent with potential roles in RNAi. Functional analysis of these novel siRNA-associated proteins sug-gests that these factors may play an important role i