Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast.
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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. |
Year of Publication | 2015
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Journal | PLoS Genet
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Volume | 11
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Issue | 5
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Pages | e1005206
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Date Published | 2015 May
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ISSN | 1553-7404
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DOI | 10.1371/journal.pgen.1005206
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PubMed ID | 25950722
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PubMed Central ID | PMC4423881
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Grant list | GM088344 / GM / NIGMS NIH HHS / United States
GM096193 / GM / NIGMS NIH HHS / United States
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