MicroRNAs can generate thresholds in target gene expression

Shankar Mukherji, Margaret S. Ebert, Grace X.Y. Zheng, John S. Tsang, Phillip A. Sharp, Alexander Van Oudenaarden

Research output: Contribution to journalArticlepeer-review

508 Scopus citations

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.

Original languageEnglish
Pages (from-to)854-859
Number of pages6
JournalNature Genetics
Volume43
Issue number9
DOIs
StatePublished - Sep 2011

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