Function of GW182 and GW bodies in siRNA and miRNA pathways.

GW182 is an 182 kDa protein with multiple glycine/tryptophan repeats (GW or WG) playing a central role in siRNA- and miRNA-mediated gene silencing. GW182 interacts with its functional partner Argonaute proteins (AGO) via multiple domains to exert its silencing activity in both pathways. In siRNA-mediated silencing, knockdown either GW182 or Ago2 causes loss of silencing activity correlating with the disassembly of GWBs. In contrast, GW182 and its longer isoform TNGW1 appear to be downstream repressors that function independent of Ago2, whereas the Ago2-GW182 interaction is critical for the localization of Ago2 in the cytoplasmic foci and its repression function. GW182 contains two non-overlapping repression domains that can trigger translational repression with mild effect on mRNA decay. Collectively, GW182 plays a critical role in miRNA-mediated gene silencing.