Ago2/miRISC-mediated inhibition of CBP80/20-dependent translation and thereby abrogation of nonsense-mediated mRNA decay require the cap-associating activity of Ago2

Junho Choe, Hana Cho, Sung-Gil Chi, Yoon Ki Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2682-2687
Number of pages6
JournalFEBS Letters
Volume585
Issue number17
DOIs
Publication statusPublished - 2011 Sep 2

Fingerprint

Nonsense Mediated mRNA Decay
Gene Silencing
MicroRNAs
Messenger RNA
RNA Cap-Binding Proteins
Factor IX
Genes
Immunoprecipitation
Antibodies

Keywords

  • Ago2
  • CBP80/20
  • eIF4E
  • MicroRNA
  • NMD

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

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title = "Ago2/miRISC-mediated inhibition of CBP80/20-dependent translation and thereby abrogation of nonsense-mediated mRNA decay require the cap-associating activity of Ago2",
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.",
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T1 - Ago2/miRISC-mediated inhibition of CBP80/20-dependent translation and thereby abrogation of nonsense-mediated mRNA decay require the cap-associating activity of Ago2

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AU - Cho, Hana

AU - Chi, Sung-Gil

AU - Kim, Yoon Ki

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N2 - 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.

AB - 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.

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