During the course of gene silencing by RNAi the destruction of target mRNA is catalysed by the siRNA-guided, RNA-induced silencing complex (RISC). RISC, composed of two signature components (siRNA/miRNA and Argonaute), is an endonuclease , which catalyses the cleavage of a single phosphodiester bond on the RNA target. The cleavage reaction requires “Mg2+, but not Ca2+, and the cleavage product termini suggest a role for Mg2+ in catalysis” (Current Biology, 2004, Vol 14: 787-791). Argonaute proteins, reported from RISC complexes of diverse organisms, are the key components of RISC. The Argonaute protein family is highly diverse, and the members contain two domains: a PAZ domain, which is involved in miRNA/siRNA binding, and a PIWI domain, which is related to RNaseH endonucleases and functions in slicer activity.