TY - GEN AB - <p>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.</p> AD - Harvard University AD - Harvard University AD - Harvard University AD - Harvard University AD - University of Chicago AU - Csárdi, Gábor AU - Franks, Alexander AU - Choi, David S. AU - Airoldi, Edoardo M. AU - Drummond, D. Allan DA - 2015-05-07 ID - 10234 JF - PLOS Genetics L1 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.zip L1 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.pdf L2 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.zip L2 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.pdf L4 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.zip L4 - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.pdf LA - eng LK - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.zip LK - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.pdf N2 - <p>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.</p> PY - 2015-05-07 T1 - Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast TI - Accounting for Experimental Noise Reveals That mRNA Levels, Amplified by Post-Transcriptional Processes, Largely Determine Steady-State Protein Levels in Yeast UR - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.zip UR - https://knowledge.uchicago.edu/record/10234/files/journal.pgen.1005206.pdf Y1 - 2015-05-07 ER -