miRNA-mediated deadenylation is orchestrated by GW182 through two conserved motifs that interact with CCR4-NOT.

miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction ...
of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT.
Mesh Terms:
Amino Acid Motifs, Animals, Autoantigens, Carrier Proteins, Exoribonucleases, HeLa Cells, Humans, MicroRNAs, Multiprotein Complexes, Protein Structure, Tertiary, RNA-Binding Proteins, RNA-Induced Silencing Complex, Transcription Factors
Nat. Struct. Mol. Biol.
Date: Nov. 01, 2011
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