Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast
Genre
Journal ArticleDate
2015-01-01Author
Csárdi, GFranks, A
Choi, DS
Airoldi, EM
Drummond, DA
Subject
Gene Expression Regulation, FungalModels, Genetic
RNA Processing, Post-Transcriptional
RNA, Messenger
Reproducibility of Results
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Transcription, Genetic
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http://hdl.handle.net/20.500.12613/5275
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10.1371/journal.pgen.1005206Abstract
© 2015 Csárdi et al. 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/5257