Human let-7a miRNA blocks protein production on actively translating polyribosomes

Nat Struct Mol Biol. 2006 Dec;13(12):1108-14. doi: 10.1038/nsmb1173. Epub 2006 Nov 26.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Humans
  • MicroRNAs / genetics*
  • Molecular Chaperones / metabolism
  • Polyribosomes / genetics
  • Polyribosomes / physiology*
  • Protein Binding
  • Protein Biosynthesis / genetics*
  • RNA, Messenger / genetics
  • Ribosomes / genetics

Substances

  • MicroRNAs
  • Molecular Chaperones
  • RNA, Messenger
  • mirnlet7 microRNA, human
  • nascent-polypeptide-associated complex