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

Christopher Rouya, Nadeem Siddiqui, Masahiro Morita, Thomas F. Duchaine, Marc R. Fabian, Nahum Sonenberg

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1398-1409
Number of pages12
JournalRNA
Volume20
Issue number9
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Gene Silencing
MicroRNAs
RNA Stability
Biological Phenomena
Peptide Initiation Factors
Messenger RNA
Protein Biosynthesis
Proteins
Mutation

Keywords

  • CCR4-NOT
  • DDX6
  • Deadenylation
  • Decapping
  • microRNA
  • mRNA decay

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Rouya, C., Siddiqui, N., Morita, M., Duchaine, T. F., Fabian, M. R., & Sonenberg, N. (2014). Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. RNA, 20(9), 1398-1409. https://doi.org/10.1261/rna.045302.114

Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. / Rouya, Christopher; Siddiqui, Nadeem; Morita, Masahiro; Duchaine, Thomas F.; Fabian, Marc R.; Sonenberg, Nahum.

In: RNA, Vol. 20, No. 9, 01.01.2014, p. 1398-1409.

Research output: Contribution to journalArticle

Rouya, C, Siddiqui, N, Morita, M, Duchaine, TF, Fabian, MR & Sonenberg, N 2014, 'Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1', RNA, vol. 20, no. 9, pp. 1398-1409. https://doi.org/10.1261/rna.045302.114
Rouya C, Siddiqui N, Morita M, Duchaine TF, Fabian MR, Sonenberg N. Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. RNA. 2014 Jan 1;20(9):1398-1409. https://doi.org/10.1261/rna.045302.114
Rouya, Christopher ; Siddiqui, Nadeem ; Morita, Masahiro ; Duchaine, Thomas F. ; Fabian, Marc R. ; Sonenberg, Nahum. / Human DDX6 effects miRNA-mediated gene silencing via direct binding to CNOT1. In: RNA. 2014 ; Vol. 20, No. 9. pp. 1398-1409.
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