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Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells
Ramesh S. Pillai,1Suvendra N. Bhattacharyya,1Caroline G. Artus,1Tabea Zoller,1Nicolas Cougot,2Eugenia Basyuk,2Edouard Bertrand,2Witold Filipowicz1*
MicroRNAs (miRNAs) are 21-nucleotide-long RNA molecules regulatinggene expression in multicellular eukaryotes. In metazoa, miRNAsact by imperfectly base-pairing with the 3' untranslated regionof target messenger RNAs (mRNAs) and repressing protein accumulationby an unknown mechanism. We demonstrate that endogenous let-7microribonucleoproteins (miRNPs) or the tethering of Argonaute(Ago) proteins to reporter mRNAs in human cells inhibit translationinitiation. M7G-cap-independent translation is not subject torepression, suggesting that miRNPs interfere with recognitionof the cap. Repressed mRNAs, Ago proteins, and miRNAs were allfound to accumulate in processing bodies. We propose that localizationof mRNAs to these structures is a consequence of translationalrepression.
1 Friedrich Miescher Institute for Biomedical Research, 4002 Basel, Switzerland. 2 Institut de Génétique Moléculaire de Montpellier, 34000 Montpellier, France.
* To whom correspondence should be addressed. E-mail: Filipowi{at}fmi.ch
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