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A simple mass-action model predicts protein timecourses from mRNA trajectories during a dynamic response in two strains of S. cerevisiae

Kuo, S.; Egertson, J.; Merrihew, G.; MacCoss, M. J.; Pollard, D.; Rifkin, S. A.

2019-10-16 genomics
10.1101/805846 bioRxiv
Show abstract

Although mRNA is a necessary precursor to protein, several studies have argued that the relationship between mRNA and protein levels is often weak. This claim undermines the functional relevance of conclusions based on quantitative analyses of mRNA levels, which are ubiquitous in modern biology from the single gene to the whole genome scale. Furthermore, if post-translational processes vary between strains and species, then comparative studies based on mRNA alone would miss an important driver of diversity. However, gene expression is dynamic, and most studies examining relationship between mRNA and protein levels at the genome scale have analyzed single timepoints. We measure yeast gene expression after pheromone exposure and show that, for most genes, protein timecourses can be predicted from mRNA timecourses through a simple, gene-specific, generative model. By comparing model parameters and predictions between strains, we find that while mRNA variation often leads to protein differences, evolution also manipulates protein-specific processes to amplify or buffer transcriptional regulation.

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