Regulation of transcriptome, translation, and proteome in response to environmental stress in fission yeast

Gene expression is controlled globally and at multiple levels in response to environmental stress, but the relationships among these dynamic regulatory changes are not clear. Here we analyzed global regulation during different stress conditions in fission yeast, Schizosaccharomyces pombe, combining dynamic genome-wide data on mRNA, translation, and protein profiles.

We observed a strong overall concordance between changes in mRNAs and co-directional changes in translation, for both induced and repressed genes, in response to three conditions: oxidative stress, heat shock, and DNA damage. However, approximately 200 genes each under oxidative and heat stress conditions showed discordant regulation with respect to mRNA and translation profiles, with genes and patterns of regulation being stress-specific. For oxidative stress, we also measured dynamic profiles for 2,147 proteins, comprising 43% of the proteome. The mRNAs induced during oxidative stress strongly correlated with increased protein expression, while repressed mRNAs did not relate to the corresponding protein profiles. Overall changes in relative protein expression correlated better with changes in mRNA expression than with changes in translational efficiency.

These data highlight a global coordination and fine-tuning of gene regulation during stress that mostly acts in the same direction at the levels of transcription and translation. In the oxidative stress condition analyzed, transcription dominates translation to control protein abundance. The concordant regulation of transcription and translation leads to the expected adjustment in protein expression only for up-regulated mRNAs. These patterns of control might reflect the need to balance protein production for stress survival given a limited translational capacity.