The Argonauteprotein family, first discovered for its evolutionarily conserved stem cell function,[1] plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the gene silencing phenomenon known as RNA interference (RNAi).[2] Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity (base pairing), which then leads to mRNA cleavage, translation inhibition, and/or the initiation of mRNA decay.[3]
The name of this protein family is derived from a mutant phenotype resulting from mutation of AGO1 in Arabidopsis thaliana, which was likened by Bohmert et al. to the appearance of the pelagic octopus Argonauta argo.[4]
Left: A full-length argonaute protein from the archaea species Pyrococcus furiosus.PDB1U04. Right: The PIWI domain of an argonaute protein in complex with double-stranded RNAPDB1YTU. The base-stacking interaction between the 5′ base on the guide strand and a conserved tyrosine residue (light blue) is highlighted; the stabilizing divalent cation (magnesium) is shown as a gray sphere.Lentiviral delivery of designed shRNA's and the mechanism of RNA interference in mammalian cells.
