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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilung 2 - Biochemistry (E. Izaurralde)     Display Documents

ID: 705459.0, MPI für Entwicklungsbiologie / Abteilung 2 - Biochemistry (E. Izaurralde)
A DDX6-CNOT1 complex and W-binding pockets in CNOT9 reveal direct links between miRNA target recognition and silencing
Authors:Chen, Y.; Boland, A.; Kuzuoglu-Ozturk, D.; Bawankar, P.; Loh, B.; Chang, C. T.; Weichenrieder, O.; Izaurralde, E.
Date of Publication (YYYY-MM-DD):2014-06-05
Title of Journal:Molecular Cell
Journal Abbrev.:Mol Cell
Issue / Number:5
Start Page:737
End Page:750
Sequence Number of Article:24768540
Review Status:Internal review
Audience:Experts Only
Abstract / Description: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.
Free Keywords:Animals; Binding Sites; Crystallography, X-Ray; DEAD-box RNA Helicases/*chemistry/metabolism; Drosophila melanogaster; HEK293 Cells; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; MicroRNAs/*genetics; Models, Molecular; Protein Binding; Protein Interaction Domains and Motifs; Protein Structure, Quaternary; Protein Structure, Secondary; Proto-Oncogene Proteins/*chemistry/metabolism; *RNA Interference; Transcription Factors/*chemistry/metabolism
External Publication Status:published
Document Type:Article
Communicated by:root
Affiliations:MPI für Entwicklungsbiologie/Abteilung 2 - Biochemie (Elisa Izaurralde)
External Affiliations:Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Electronic address: oliver.weichenrieder@tuebingen.mpg.de. Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tubingen, Germany. Electronic address: elisa.izaurralde@tuebingen.mpg.de.
Identifiers:ISSN:1097-4164 (Electronic) 1097-2765 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/24768540 [ID No:2]
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