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 journalArticlepeer-review

    20 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 Sept 2

    Bibliographical note

    Funding Information:
    We thank Witold Filipowicz and Zissimos Mourelatos for providing Ago2-tethering plasmids and Marvin J. Fritzler for α-GW182 antibody. This work was supported by the Korea Science and Engineering Foundation (KOSEF) Grant funded by the Korea government (MEST) ( 2009-0084897 , and 0001197 ) and the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) ( KRF-2008-314-C00247 ).

    Keywords

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

    ASJC Scopus subject areas

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

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