MicroRNAs can generate thresholds in target gene expression

Nat Genet. 2011 Aug 21;43(9):854-9. doi: 10.1038/ng.905.

Abstract

MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression.

Publication types

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

MeSH terms

  • Binding Sites
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation*
  • Gene Targeting*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Luciferases / genetics
  • MicroRNAs / genetics*
  • Microscopy, Fluorescence

Substances

  • MicroRNAs
  • Luciferases