FIGURE 6.

Model for miRNA-mediated gene silencing. RISC is represented as a complex minimally including an Argonaute protein (green) and GW182 (cyan). GW182 proteins contain an N-terminal AGO-binding domain, which provides multiple binding sites for Argonaute proteins and a bipartite C-terminal silencing domain (SD), which promotes translational repression and decay of mRNA targets. Note that at least in D. melanogaster GW182, the AGO-binding domain exhibits strong silencing activity in tethering assays and complements silencing in cells lacking endogenous GW182, indicating that in addition to interacting with AGO1, this domain contributes to the assembly of repressive complexes (Chekulaeva et al. 2009). Overexpressing this domain alone in wild-type cells inhibits silencing in a dominant negative manner (Till et al. 2007; Eulalio et al. 2008b; Chekulaeva et al. 2009; Iwasaki et al. 2009; Takimoto et al. 2009).