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1: Nat Struct Mol Biol. 2006 Dec;13(12):1108-14. Epub 2006 Nov 26.
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Human let-7a miRNA blocks protein production on actively translating polyribosomes.

Nottrott S, Simard MJ, Richter JD.

Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St., Suite 204, Worcester, Massachusetts 01605, USA.

MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level through base-pairing to 3' untranslated regions (UTRs) of messenger RNAs. The mechanism by which human let-7a miRNA regulates mRNA translation was examined in HeLa cells expressing reporter mRNAs containing the Caenorhabditis elegans lin-41 3' UTR. let-7a miRNA strongly repressed translation, yet the majority of control and lin-41-bearing RNAs sedimented with polyribosomes in sucrose gradients; these polyribosomes, together with let-7a miRNA and the miRISC protein AGO, were released from those structures by puromycin. RNA containing the lin-41 3' UTR and an iron response element in the 5' UTR sedimented with polysomes when cells were incubated with iron, but showed ribosome run-off when the iron was chelated. These data indicate that let-7a miRNA inhibits actively translating polyribosomes. Nascent polypeptide coimmunoprecipitation experiments further suggest that let-7a miRNA interferes with the accumulation of growing polypeptides.

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PMID: 17128272 [PubMed - indexed for MEDLINE]