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MicroRNAs can generate thresholds in target gene expression.

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.

Pubmed ID: 21857679

Authors

  • Mukherji S
  • Ebert MS
  • Zheng GX
  • Tsang JS
  • Sharp PA
  • van Oudenaarden A

Journal

Nature genetics

Publication Data

September 29, 2011

Associated Grants

  • Agency: NIH HHS, Id: 1DP1OD003936
  • Agency: NCI NIH HHS, Id: DP1 CA174420
  • Agency: NIH HHS, Id: DP1 OD003936
  • Agency: NIH HHS, Id: DP1 OD003936-02
  • Agency: NIH HHS, Id: DP1 OD003936-03
  • Agency: NCI NIH HHS, Id: P01-CA42063
  • Agency: NCI NIH HHS, Id: P30-CA14051
  • Agency: NCI NIH HHS, Id: R01-CA133404
  • Agency: NIGMS NIH HHS, Id: R01-GM34277
  • Agency: NCI NIH HHS, Id: U54 CA143874
  • Agency: NCI NIH HHS, Id: U54 CA143874-02
  • Agency: NCI NIH HHS, Id: U54CA143874
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

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