Unknown

Dataset Information

0

Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1.


ABSTRACT: 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.

SUBMITTER: Rouya C 

PROVIDER: S-EPMC4138323 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1.

Rouya Christopher C   Siddiqui Nadeem N   Morita Masahiro M   Duchaine Thomas F TF   Fabian Marc R MR   Sonenberg Nahum N  

RNA (New York, N.Y.) 20140717 9


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  ...[more]

Similar Datasets

| S-EPMC9534413 | biostudies-literature
| S-EPMC3018788 | biostudies-literature
| S-EPMC3147021 | biostudies-literature
| S-EPMC2000321 | biostudies-literature
| S-EPMC2685099 | biostudies-literature
| S-EPMC3971879 | biostudies-literature
| S-EPMC3230379 | biostudies-literature
| S-EPMC5499809 | biostudies-other
| S-SCDT-10_15252-EMBR_202357250 | biostudies-other
| S-SCDT-10_1038-S44318-024-00249-4 | biostudies-other