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  Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression

Mathys, H., Basquin, J., Ozgur, S., Czarnocki-Cieciura, M., Bonneau, F., Aartse, A., et al. (2014). Structural and Biochemical Insights to the Role of the CCR4-NOT Complex and DDX6 ATPase in MicroRNA Repression. MOLECULAR CELL, 54(5), 751-765. doi:10.1016/j.molcel.2014.03.036.

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 Creators:
Mathys, Hansruedi1, Author
Basquin, Jerome2, Author              
Ozgur, Sevim2, Author              
Czarnocki-Cieciura, Mariusz1, Author
Bonneau, Fabien2, Author              
Aartse, Aafke1, Author
Dziembowski, Andrzej1, Author
Nowotny, Marcin1, Author
Conti, Elena2, Author              
Filipowicz, Witold1, Author
Affiliations:
1external, ou_persistent22              
2Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              

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Free keywords: DEAD-BOX PROTEIN; MESSENGER-RNA DECAY; TRANSLATIONAL REPRESSION; CRYSTAL-STRUCTURE; GW182 PROTEINS; DEADENYLASE COMPLEX; BINDING-PROPERTIES; MIRNA TARGETS; HELICASE; REVEALS
 Abstract: MicroRNAs (miRNAs) control gene expression by regulating mRNA translation and stability. The CCR4-NOT complex is a key effector of miRNA function acting downstream of GW182/TNRC6 proteins. We show that miRNA-mediated repression requires the central region of CNOT1, the scaffold protein of CCR4-NOT. A CNOT1 domain interacts with CNOT9, which in turn interacts with the silencing domain of TNRC6 in a tryptophan motif-dependent manner. These interactions are direct, as shown by the structure of a CNOT9-CNOT1 complex with bound tryptophan. Another domain of CNOT1 with an MIF4G fold recruits the DEAD-box ATPase DDX6, a known translational inhibitor. Structural and biochemical approaches revealed that CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity. Structure-based mutations showed that the CNOT1 MIF4G-DDX6 interaction is important for miRNA-mediated repression. These findings provide insights into the repressive steps downstream of the GW182/TNRC6 proteins and the role of the CCR4-NOT complex in posttranscriptional regulation in general.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: MOLECULAR CELL
Source Genre: Journal
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Publ. Info: 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 54 (5) Sequence Number: - Start / End Page: 751 - 765 Identifier: ISSN: 1097-2765