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Global quantification of mammalian gene expression control

A Corrigendum to this article was published on 13 February 2013

This article has been updated

Abstract

Gene expression is a multistep process that involves the transcription, translation and turnover of messenger RNAs and proteins. Although it is one of the most fundamental processes of life, the entire cascade has never been quantified on a genome-wide scale. Here we simultaneously measured absolute mRNA and protein abundance and turnover by parallel metabolic pulse labelling for more than 5,000 genes in mammalian cells. Whereas mRNA and protein levels correlated better than previously thought, corresponding half-lives showed no correlation. Using a quantitative model we have obtained the first genome-scale prediction of synthesis rates of mRNAs and proteins. We find that the cellular abundance of proteins is predominantly controlled at the level of translation. Genes with similar combinations of mRNA and protein stability shared functional properties, indicating that half-lives evolved under energetic and dynamic constraints. Quantitative information about all stages of gene expression provides a rich resource and helps to provide a greater understanding of the underlying design principles.

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Figure 1: Parallel quantification of mRNA and protein turnover and levels.
Figure 2: mRNA and protein levels and half-lives.
Figure 3: Quantitative model of gene expression in growing cells.
Figure 4: Impact of different rates and rate constants on protein abundance.
Figure 5: Functional characteristics of genes with different mRNA and protein half-lives.

Accession codes

Primary accessions

Sequence Read Archive

Data deposits

Sequences have been deposited in the Sequence Read Archive under accession code SRA030871.

Change history

  • 13 February 2013

    Nature 473, 337–342 (2011); doi:10.1038/nature10098 Mark Biggin of the Lawrence Berkeley National Laboratory contacted us, noting that our mass-spectrometry-based protein copy number estimates are lower than several literature-based values. We therefore re-analysed the scripts used for data processing, and found a scaling error that occurred during the conversion of normalized protein intensity values into absolute copy number estimates.

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Acknowledgements

We thank N. Rajewsky and L. Dölken for fruitful discussions and C. Sommer for technical assistance. M.S. and W.C. are supported by the Helmholtz Association, the German Ministry of Education and Research (BMBF) and the Senate of Berlin by funds aimed at establishing the Berlin Institute of Medical Systems Biology (BIMSB) (grant number 315362A). J.W. is supported by the ForSys-programme of the German Ministry of Education and Research (grant number 315289); D.B. by the Helmholtz Alliance on Systems Biology/MSBN; and N.L. by the China Scholarship Council CSC.

Author information

Authors and Affiliations

Authors

Contributions

M.S. conceived, designed and supervised the experiments. B.S. performed wet-lab experiments, mass spectrometry and proteomic data analysis. D.B. and J.W. developed and employed the mathematical model. N.L. performed RNA-seq experiments. W.C. designed and supervised RNA-seq experiments. B.S., D.B., J.S., W.C. and M.S. analysed genome-wide data. G.D. helped in cycloheximide chase experiments and data analysis. B.S., D.B., J.S., J.W., W.C. and M.S. interpreted the data. M.S. wrote the manuscript.

Corresponding authors

Correspondence to Jana Wolf, Wei Chen or Matthias Selbach.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-12 with legends. This file was replaced on 13 February 2013 - see Selbach 11848 corrigendum for details. (PDF 2430 kb)

Supplementary Methods

This file contains Supplementary Methods and Data, Supplementary Figures 1-4 with legends and additional references. (PDF 739 kb)

Supplementary Table 1

This table displays an overview of data reproducibility. This file was replaced on 13 February 2013 - see Selbach 11848 corrigendum for details. (XLS 31 kb)

Supplementary Table 2

This table displays categories enriched in bins of genes with the specified combinations of protein and mRNA half-lives. (XLS 72 kb)

Supplementary Table 3

This table displays protein and mRNA copy numbers, half-lives, transcription rates and translation rate constants in mouse fibroblasts (NIH 3T3). This file was replaced on 13 February 2013 - see Selbach 11848 corrigendum for details. (XLS 3314 kb)

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Schwanhäusser, B., Busse, D., Li, N. et al. Global quantification of mammalian gene expression control. Nature 473, 337–342 (2011). https://doi.org/10.1038/nature10098

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