Abstract
Nuclear cap-binding protein (CBP) 80/20-dependent translation (CT) is one of the targets for miRNA-mediated gene silencing. Here, we provide evidence that human argonaute 2 (Ago2) competes with CBP80/20 for cap-association, inhibiting CT and thus nonsense-mediated mRNA decay (NMD), which is tightly coupled to CT. Tethering of Ago2, but not of Ago2F2V2 which lacks cap-association activity, to the 3'UTR of PTC-containing mRNA abrogates NMD. Immunoprecipitation using CBP80 antibody reveals that Ago2, but not Ago2F2V2, inhibits the binding of CBP80/20 to cap structure. Our observations provide molecular insight into the cross-talk between miRNA-mediated gene silencing, CT, and NMD.
Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions / genetics
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Animals
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Argonaute Proteins
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Blotting, Western
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COS Cells
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Chlorocebus aethiops
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Eukaryotic Initiation Factor-2 / genetics
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Eukaryotic Initiation Factor-2 / metabolism*
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Eukaryotic Initiation Factor-4E / genetics
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Eukaryotic Initiation Factor-4E / metabolism
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HeLa Cells
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Humans
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Immunoprecipitation
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MicroRNAs / genetics
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Nuclear Cap-Binding Protein Complex / genetics
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Nuclear Cap-Binding Protein Complex / metabolism*
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Protein Binding
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Protein Biosynthesis
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RNA Stability / genetics*
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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3' Untranslated Regions
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AGO2 protein, human
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Argonaute Proteins
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Eukaryotic Initiation Factor-2
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Eukaryotic Initiation Factor-4E
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MicroRNAs
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Nuclear Cap-Binding Protein Complex