Structural insights into the human GW182-PABC interaction in microRNA-mediated deadenylation

GW182-family proteins are essential for microRNA-mediated translational repression and deadenylation in animal cells. Here we show that a conserved motif in the human GW182 paralog TNRC6C interacts with the C-terminal domain of polyadenylate binding protein 1 (PABC) and present the crystal structure of the complex. Mutations at the complex interface impair mRNA deadenylation in mammalian cell extracts, suggesting that the GW182-PABC interaction contributes to microRNA-mediated gene silencing. MicroRNAs (miRNAs) are short endogenous RNAs that regulate a variety of eukaryotic cell processes, including cell growth, proliferation and differentiation. In Metazoa, miRNAs associate with Argonaute (Ago) proteins in miRNA-induced silencing complexes (miRISCs) to silence target mRNAs by a mechanism involving translational repression and concurrent stimulation of mRNA deadenylation and subsequent degradation1, 2. In addition to Ago proteins, miRNA-mediated silencing requires proteins of the GW182 family3. Tethering of GW182 proteins to mRNA reporters induces translational repression and mRNA decay in the absence of miRNAs and Ago, suggesting that GW182 proteins have silencing functions downstream of Ago4. A direct interaction between Ago and GW182, Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use