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MicroRNAs can generate thresholds in target gene expression.

Nature genetics | Sep 29, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21857679

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 RIS Download

Mesh terms: Binding Sites | Flow Cytometry | Gene Expression | Gene Expression Regulation | Gene Targeting | Genes, Reporter | HeLa Cells | Humans | Luciferases | MicroRNAs | Microscopy, Fluorescence

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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:

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