A Ddx6-Cnot1 Complex and W-Binding Pockets in Cnot9 Reveal Direct Links between Mirna Target Recognition and Silencing

作者: Ying Chen , Andreas Boland , Duygu Kuzuoğlu-Öztürk , Praveen Bawankar , Belinda Loh

DOI: 10.1016/J.MOLCEL.2014.03.034

关键词: GeneticsPlasma protein bindingProtein subunitBiologyCCR4-NOT complexProtein structureCell biologyEffectorRNA interferenceRegulation of gene expressionGene silencing

摘要: CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It recruited to miRNA targets through interactions with tryptophan (W)-containing motifs TNRC6/GW182 proteins and required for both translational repression degradation of targets. Here, we elucidate the structural basis repressive activity its interaction TNRC6/GW182s. We show that conserved CNOT9 subunit attaches domain unknown function (DUF3819) CNOT1 scaffold. The resulting provides binding sites TNRC6/GW182, crystal structure reveals tandem W-binding pockets located CNOT9. further MIF4G interacts C-terminal RecA DDX6, repressor decapping activator. this demonstrates striking similarity eIF4G-eIF4A complex. Together, our data provide missing physical links molecular pathway connects target recognition repression, deadenylation, decapping.

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