A molecular link between miRISCs and deadenylases provides new insight into the mechanism of gene silencing by microRNAs.

MicroRNAs (miRNAs) are a large family of endogenous noncoding RNAs that, together with the Argonaute family of proteins (AGOs), silence the expression of complementary mRNA targets posttranscriptionally. Perfectly complementary targets are cleaved within the base-paired region by catalytically active AGOs. In the case of partially complementary targets, however, AGOs are insufficient for silencing and need to recruit a protein of the GW182 family. GW182 proteins induce translational repression, mRNA deadenylation and exonucleolytic target degradation. Recent work has revealed a direct molecular link between GW182 proteins and cellular deadenylase complexes. These findings shed light on how miRNAs bring about target mRNA degradation and promise to further our understanding of the mechanism of miRNA-mediated repression.