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 [].
FAM172A plays an important role in the regulation of cotranscriptional alternative splicing by interacting with Ago2 (Argonaute-2) and Chd7. The FAM172A mutant mice display a complex phenotype mimicking both the major and minor features of CHARGE syndrome (CHARGES) [].
MOV-10 (moloney leukemia virus 10 protein) is the human homologue of Drosophila melanogaster Armitage (armi). Human MOV-10 is a 5' to 3' RNA helicase required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC) [, , ]. It has been shown to interact with fragile X messenger ribonucleoprotein 1 (FMRP) and regulates miRNA-mediated translational repression by AGO2 []. Interestingly, it interacts with retrotransposons and acts as a potent inhibitor of retrotransposition in cells []. MOV-10 is required for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). It interacts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription [].
