Eukaryotic Argonautes come into focus

Despite the fact that different classes of small RNAs are generated by largely different biogenesis pathways, all mature small RNAs associate with an Argonaute family member to form the RNA-induced silencing complex (RISC). Gene silencing by RISC could not be studied in molecular detail because structural information on eukaryotic Argonautes was lacking. Recently, however, the structure of human Argonaute-2 (hAgo2), a model for RISC function, was determined in complexes with heterogeneous guide RNA and in complexes with a specific miRNA. We review the exciting advances that these two structures, together with the structure of a budding yeast Argonaute, brought to the field of eukaryotic RNA interference (RNAi), and how they will enable a more detailed mechanistic understanding of eukaryotic RISC. Despite the fact that different classes of small RNAs are generated by largely different biogenesis pathways, all mature small RNAs associate with an Argonaute family member to form the RNA-induced silencing complex (RISC). Gene silencing by RISC could not be studied in molecular detail because structural information on eukaryotic Argonautes was lacking. Recently, however, the structure of human Argonaute-2 (hAgo2), a model for RISC function, was determined in complexes with heterogeneous guide RNA and in complexes with a specific miRNA. We review the exciting advances that these two structures, together with the structure of a budding yeast Argonaute, brought to the field of eukaryotic RNA interference (RNAi), and how they will enable a more detailed mechanistic understanding of eukaryotic RISC.