Abstract
miRNAs recruit the miRNA-induced silencing complex (miRISC), which includes Argonaute and GW182 as core proteins. GW182 proteins effect translational repression and deadenylation of target mRNAs. However, the molecular mechanisms of GW182-mediated repression remain obscure. We show here that human GW182 independently interacts with the PAN2-PAN3 and CCR4-NOT deadenylase complexes. Interaction of GW182 with CCR4-NOT is mediated by two newly discovered phylogenetically conserved motifs. Although either motif is sufficient to bind CCR4-NOT, only one of them can promote processive deadenylation of target mRNAs. Thus, GW182 serves as both a platform that recruits deadenylases and as a deadenylase coactivator that facilitates the removal of the poly(A) tail by CCR4-NOT.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Autoantigens / chemistry
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Autoantigens / genetics
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Autoantigens / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Exoribonucleases / genetics
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Exoribonucleases / metabolism
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HeLa Cells
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Humans
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Multiprotein Complexes / chemistry
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Multiprotein Complexes / metabolism*
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Protein Structure, Tertiary
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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RNA-Induced Silencing Complex / genetics
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RNA-Induced Silencing Complex / metabolism*
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Autoantigens
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CNOT1 protein, human
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Carrier Proteins
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MicroRNAs
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Multiprotein Complexes
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PAN3 protein, human
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RNA-Binding Proteins
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RNA-Induced Silencing Complex
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TNRC6A protein, human
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Transcription Factors
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Exoribonucleases
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PAN2 protein, human