Argonaute MID domain takes centre stage

Argonaute (AGO) proteins are the central component of small RNA-mediated gene silencing in eukaryotes. Functional AGO complexes are loaded with single-stranded small RNAs, which guide AGO to a messenger RNA (mRNA) target through base pairing. Although the structure of a full-length eukaryotic AGO has yet to be described, insights into the mechanism of guide RNA binding and target recognition have been revealed by the structures of distantly related AGO homologues from archaea and eubacteria (Song et al, 2004; Wang et al, 2008, 2009). These studies show that AGO proteins are composed of amino-terminal, PAZ (PIWI/Argonaute/Zwille), MID (middle) and PIWI (P-element-induced whimpy testes) domains. The phosphorylated 5′-end of the guide strand RNA is localized in the MID–PIWI domain interface with the 3′-end anchored to the PAZ domain. On binding to mRNA the catalytic RNase H-like active site located in the PIWI domain is in position to cleave the targeted mRNA