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 language | English |
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Pages (from-to) | 2682-2687 |
Number of pages | 6 |
Journal | FEBS Letters |
Volume | 585 |
Issue number | 17 |
DOIs | |
Publication status | Published - 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