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miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs

Item Type:Article
Title:miRNA repression involves GW182-mediated recruitment of CCR4-NOT through conserved W-containing motifs
Creators Name:Chekulaeva, M. and Mathys, H. and Zipprich, J.T. and Attig, J. and Colic, M. and Parker, R. and Filipowicz, W.
Abstract:miRNA-mediated repression in animals is dependent on the GW182 protein family. GW182 proteins are recruited to the miRNA repression complex through direct interaction with Argonaute proteins, and they function downstream to repress target mRNA. Here we demonstrate that in human and Drosophila melanogaster cells, the critical repressive features of both the N-terminal and C-terminal effector domains of GW182 proteins are Gly/Ser/Thr-Trp (G/S/TW) or Trp-Gly/Ser/Thr (WG/S/T) motifs. These motifs, which are dispersed across both domains and act in an additive manner, function by recruiting components of the CCR4-NOT deadenylation complex. A heterologous yeast polypeptide with engineered WG/S/T motifs acquired the ability to repress tethered mRNA and to interact with the CCR4-NOT complex. These results identify previously unknown effector motifs functioning as important mediators of miRNA-induced silencing in both species, and they reveal that recruitment of the CCR4-NOT complex by tryptophan-containing motifs acts downstream of GW182 to repress mRNAs, including inhibiting translation independently of deadenylation.
Keywords:Amino Acid Motifs, Autoantigens, Drosophila Proteins, Gene Silencing, HEK293 Cells, MicroRNAs, Multiprotein Complexes, RNA-Binding Proteins, RNA-Induced Silencing Complex, Tertiary Protein Structure, Transcription Factors, Animals, Drosophila melanogaster
Source:Nature Structural & Molecular Biology
Publisher:Nature Publishing Group
Page Range:1218-1226
Date:7 October 2011
Official Publication:https://doi.org/10.1038/nsmb.2166
PubMed:View item in PubMed

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