Drs. Elisavet Maniataki and Zissimos Mourelatos (UPENN School of Medicine) report on the pathway of human RISC assembly from pre-microRNAs (miRNAs), highlighting important differences from the siRNA-fueled RISC assembly pathway in Drosophila. The authors identified a protein complex between Dicer and Argo2 - the "microRNA loading complex" (miRLC) - that lacks miRNAs. Without a requirement for ATP, miRLC catalyzes RISC assembly and disassembly to release the miRNP. "This study demonstrates that, in humans, pre-miRNA processing is coupled with RISC/miRNP assembly and involves a preformed protein complex that catalyzes all steps that constitute the cytoplasmic phase of RNAi," explains Dr. Mourelatos.