Argonaute proteins are involved in RNA interference (RNAi) and microRNA (miRNA) pathways. They can be classified into three paralogous groups: Argonaute-like proteins, which are similar to Arabidopsis thaliana AGO1; Piwi-like proteins, which are closely related to D. melanogaster PIWI (P-element induced wimpy testis); and the Caenorhabditis elegans-specific group 3 Argonautes []. Protein argonaute-2 (AGO2) belongs to the first group (Argonaute-like proteins). It is a component of the RNA-induced silencing complex (RISC) that functions in RNA-mediated gene silencing (RNAi) [, ]. AGO2 is the catalytic engine that drives mRNA cleavage in the RNAi pathway []. AGO2 suffers a phosphorylation cycle that is triggered by target engagement and negatively regulates target association, which is essential to maintain the global efficiency of miRNA-mediated silencing []. It is also the primary AGO variant involved in modulating expression of progesterone receptor by antigene RNAs []. AGO1 and AGO2 reside in three complexes with distinct Dicer and RNA-induced silencing complex activities []. The structure of AGO2 has been solved [].
