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Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast

Gábor Csárdi, Alexander Franks, David S. Choi, Edoardo M. Airoldi, D. Allan Drummond
doi: https://doi.org/10.1101/009472
Gábor Csárdi
1Dept. of Statistics, Harvard University, Cambridge, MA, USA
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Alexander Franks
1Dept. of Statistics, Harvard University, Cambridge, MA, USA
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David S. Choi
1Dept. of Statistics, Harvard University, Cambridge, MA, USA
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Edoardo M. Airoldi
1Dept. of Statistics, Harvard University, Cambridge, MA, USA
2The Broad Institute of Harvard & MIT, Cambridge, MA, USA
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D. Allan Drummond
3Dept. of Biochemistry & Molecular Biology, University of Chicago, Chicago, IL, USA
4Dept. of Human Genetics, University of Chicago, Chicago, IL, USA
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Abstract

Cells respond to their environment by modulating protein levels through mRNA transcription and post-transcriptional control. Modest observed correlations between global steady-state mRNA and protein measurements have been interpreted as evidence that mRNA levels determine roughly 40% of the variation in protein levels, indicating dominant post-transcriptional effects. However, the techniques underlying these conclusions, such as correlation and regression, yield biased results when data are noisy, missing systematically, and collinear—properties of mRNA and protein measurements—which motivated us to revisit this subject. Noise-robust analyses of 24 studies of budding yeast reveal that mRNA levels explain more than 85% of the variation in steady-state protein levels. Protein levels are not proportional to mRNA levels, but rise much more rapidly. Regulation of translation suffices to explain this nonlinear effect, revealing post-transcriptional amplification of, rather than competition with, transcriptional signals. These results substantially revise widely credited models of protein-level regulation, and introduce multiple noise-aware approaches essential for proper analysis of many biological phenomena.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 26, 2014.
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Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast
Gábor Csárdi, Alexander Franks, David S. Choi, Edoardo M. Airoldi, D. Allan Drummond
bioRxiv 009472; doi: https://doi.org/10.1101/009472
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Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast
Gábor Csárdi, Alexander Franks, David S. Choi, Edoardo M. Airoldi, D. Allan Drummond
bioRxiv 009472; doi: https://doi.org/10.1101/009472

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