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Science 17 March 2006:
Vol. 311. no. 5767, pp. 1600 - 1603
DOI: 10.1126/science.1119623
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Reports

Probing Gene Expression in Live Cells, One Protein Molecule at a Time

Ji Yu,1* Jie Xiao,1* Xiaojia Ren,1 Kaiqin Lao,2 X. Sunney Xie1{dagger}

We directly observed real-time production of single protein molecules in individual Escherichia coli cells. A fusion protein of a fast-maturing yellow fluorescent protein (YFP) and a membrane-targeting peptide was expressed under a repressed condition. The membrane-localized YFP can be detected with single-molecule sensitivity. We found that the protein molecules are produced in bursts, with each burst originating from a stochastically transcribed single messenger RNA molecule, and that protein copy numbers in the bursts follow a geometric distribution. The quantitative study of low-level gene expression demonstrates the potential of single-molecule experiments in elucidating the workings of fundamental biological processes in living cells.

1 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
2 Applied Biosystems, Foster City, CA 94404, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: xie{at}chemistry.harvard.edu

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