MicroRNAs can generate thresholds in target gene expression
Name
Sharp_MicroRNAs can.pdf
Size
1.26 MB
Format
Adobe PDF
Checksum (MD5)
34da05854d7a1be2030a1257d628876a
Author(s)
Mukherji, Shankar
Ebert, Margaret S.
Sharp, Phillip A.
van Oudenaarden, Alexander
Tsang, John S.
Zheng, Xinying Grace
Date Issued
August 2011
Journal
Nature Genetics
Publisher
Nature Publishing Group
Citation
Mukherji, Shankar et al. “MicroRNAs Can Generate Thresholds in Target Gene Expression.” Nature Genetics 43.9 (2011): 854–859.
Version
Author's final manuscript
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike 3.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/ng.905
