Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells
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- 2 September 2005
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 309 (5740) , 1573-1576
- https://doi.org/10.1126/science.1115079
Abstract
MicroRNAs (miRNAs) are ∼21-nucleotide-long RNA molecules regulating gene expression in multicellular eukaryotes. In metazoa, miRNAs act by imperfectly base-pairing with the 3′ untranslated region of target messenger RNAs (mRNAs) and repressing protein accumulation by an unknown mechanism. We demonstrate that endogenous let-7 microribonucleoproteins (miRNPs) or the tethering of Argonaute (Ago) proteins to reporter mRNAs in human cells inhibit translation initiation. M7G-cap-independent translation is not subject to repression, suggesting that miRNPs interfere with recognition of the cap. Repressed mRNAs, Ago proteins, and miRNAs were all found to accumulate in processing bodies. We propose that localization of mRNAs to these structures is a consequence of translational repression.Keywords
This publication has 25 references indexed in Scilit:
- Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodiesNature Cell Biology, 2005
- A New Paradigm for Translational Control: Inhibition via 5′-3′ mRNA Tethering by Bicoid and the eIF4E Cognate 4EHPCell, 2005
- Assay for the transbilayer movement of polyisoprenoid-linked saccharides based on the transport of water-soluble analoguesMethods, 2005
- RAS Is Regulated by the let-7 MicroRNA FamilyPublished by Elsevier ,2005
- Involvement of MicroRNA in AU-Rich Element-Mediated mRNA InstabilityCell, 2005
- Processing bodies require RNA for assembly and contain nontranslating mRNAsRNA, 2005
- Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAsNature, 2005
- Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesisRNA, 2004
- MicroRNAsCell, 2004
- Decapping and Decay of Messenger RNA Occur in Cytoplasmic Processing BodiesScience, 2003