Extensive post-transcriptional buffering of gene expression in the response to severe oxidative stress in baker’s yeast

Cells responds to diverse stimuli by changing the levels of specific effector proteins. These changes are usually examined using high throughput RNA sequencing data (RNA-Seq); transcriptional regulation is generally assumed to directly influence protein abundances. However, the correlation between RNA-Seq and proteomics data is in general quite limited owing to differences in protein stability and translational regulation. Here we perform RNA-Seq, ribosome profiling and proteomics analyses in baker's yeast cells grown in rich media and oxidative stress conditions to examine gene expression regulation at various levels. With the exception of a small set of genes involved in the maintenance of the redox state, which are regulated at the transcriptional level, modulation of protein expression is largely driven by changes in the relative ribosome density across conditions. The majority of shifts in mRNA abundance are compensated by changes in the opposite direction in the number of translating ribosomes and are predicted to result in no net change at the protein level. We also identify a subset of mRNAs which is likely to undergo specific translational repression during stress and which includes cell cycle control genes. The study suggests that post-transcriptional buffering of gene expression may be more common than previously anticipated. The work was funded by grants BFU2015–65235-P, BFU2015-68351-P and BFU2016-80039-R, from Ministerio de Economía e Innovación (Spanish Government) - FEDER (EU), and from grant PT17/0009/0014 from Instituto de Salud Carlos III – FEDER. We also received funding from the “Maria de Maeztu” Programme for Units of Excellence in R&D (MDM-2014-0370) and from Agència de Gestió d’Ajuts Universitaris i de Recerca Generalitat de Catalunya (AGAUR), grant number 2014SGR1121, 2014SGR0974, 2017SGR01020 and, predoctoral fellowship (FI) to W.B. We also acknowledge support from the EU Erasmus Programme to T.T.