Document Detail


Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1.
MedLine Citation:
PMID:  25035296     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
MicroRNAs (miRNAs) play critical roles in a variety of biological processes through widespread effects on protein synthesis. Upon association with the miRNA-induced silencing complex (miRISC), miRNAs repress target mRNA translation and accelerate mRNA decay. Degradation of the mRNA is initiated by shortening of the poly(A) tail by the CCR4-NOT deadenylase complex followed by the removal of the 5' cap structure and exonucleolytic decay of the mRNA. Here, we report a direct interaction between the large scaffolding subunit of CCR4-NOT, CNOT1, with the translational repressor and decapping activator protein, DDX6. DDX6 binds to a conserved CNOT1 subdomain in a manner resembling the interaction of the translation initiation factor eIF4A with eIF4G. Importantly, mutations that disrupt the DDX6-CNOT1 interaction impair miRISC-mediated gene silencing in human cells. Thus, CNOT1 facilitates recruitment of DDX6 to miRNA-targeted mRNAs, placing DDX6 as a downstream effector in the miRNA silencing pathway.
Authors:
Christopher Rouya; Nadeem Siddiqui; Masahiro Morita; Thomas F Duchaine; Marc R Fabian; Nahum Sonenberg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-17
Journal Detail:
Title:  RNA (New York, N.Y.)     Volume:  -     ISSN:  1469-9001     ISO Abbreviation:  RNA     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9509184     Medline TA:  RNA     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 Rouya et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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