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.
S. cerevisiae raw mRNA and protein measurements
Raw mRNA and protein measurements for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-raw.txt
S. cerevisiae log-transformed SCM-normalized mRNA and protein measurements
SCM-normalized mRNA and protein measurements for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-normalized.txt
S. cerevisiae SCM estimates of mRNA and protein levels, log-transformed and unscaled
SCM estimates of mRNA and protein levels, log-transformed and unscaled, for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-unscaled-estimate.txt
S. cerevisiae log-transformed SCM-normalized mRNA and protein measurements, with imputed values
SCM-normalized mRNA and protein measurements, with imputed values, for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-normalized-imputed.txt
S. cerevisiae SCM estimates of mRNA and protein levels, log-transformed and unscaled
SCM estimates of mRNA and protein levels, log-transformed and unscaled, for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-unscaled-estimate.txt
Ribosome density, mRNA level, and translational efficiency measurements for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
Measurements and summary statistics for RNA-seq mRNA levels, ribosome footprint density, and translational efficiency for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-translational-efficiency.txt
S. cerevisiae sampled absolute mRNA and protein levels, scaled to (average) molecules per haploid cell, sampled from SCM estimates
mRNA and protein levels, scaled to (average) molecules per haploid cell, sampled according to SCM estimates, for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-absolute-estimate-sample.txt
S. cerevisiae absolute mRNA and protein levels, scaled to (average) molecules per haploid cell, estimated by SCM
SCM estimates of absolute mRNA and protein levels, scaled to (average) molecules per haploid cell, for haploid budding yeast (S.cerevisiae) growing exponentially in rich medium with glucose
scer-mrna-protein-absolute-estimate.txt