Abstract:
:CCR4-NOT is a major effector complex in miRNA-mediated gene silencing. It is recruited to miRNA targets through interactions with tryptophan (W)-containing motifs in TNRC6/GW182 proteins and is required for both translational repression and degradation of miRNA targets. Here, we elucidate the structural basis for the repressive activity of CCR4-NOT and its interaction with TNRC6/GW182s. We show that the conserved CNOT9 subunit attaches to a domain of unknown function (DUF3819) in the CNOT1 scaffold. The resulting complex provides binding sites for TNRC6/GW182, and its crystal structure reveals tandem W-binding pockets located in CNOT9. We further show that the CNOT1 MIF4G domain interacts with the C-terminal RecA domain of DDX6, a translational repressor and decapping activator. The crystal structure of this complex demonstrates striking similarity to the eIF4G-eIF4A complex. Together, our data provide the missing physical links in a molecular pathway that connects miRNA target recognition with translational repression, deadenylation, and decapping.
journal_name
Mol Celljournal_title
Molecular cellauthors
Chen Y,Boland A,Kuzuoğlu-Öztürk D,Bawankar P,Loh B,Chang CT,Weichenrieder O,Izaurralde Edoi
10.1016/j.molcel.2014.03.034subject
Has Abstractpub_date
2014-06-05 00:00:00pages
737-50issue
5eissn
1097-2765issn
1097-4164pii
S1097-2765(14)00267-6journal_volume
54pub_type
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