Accounting for Experimental Noise Reveals That mRNA Levels,Amplified by Post-Transcriptional Processes,Largely Determine Steady-State Protein Levels in Yeast

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. © 2015 csárdi et al.