A dynamic model of proteome changes reveals new roles for transcript alteration in yeast
Open Access
- 1 January 2011
- journal article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 7 (1), 514
- https://doi.org/10.1038/msb.2011.48
Abstract
The transcriptome and proteome change dynamically as cells respond to environmental stress; however, prior proteomic studies reported poor correlation between mRNA and protein, rendering their relationships unclear. To address this, we combined high mass accuracy mass spectrometry with isobaric tagging to quantify dynamic changes in ∼2500 Saccharomyces cerevisiae proteins, in biological triplicate and with paired mRNA samples, as cells acclimated to high osmolarity. Surprisingly, while transcript induction correlated extremely well with protein increase, transcript reduction produced little to no change in the corresponding proteins. We constructed a mathematical model of dynamic protein changes and propose that the lack of protein reduction is explained by cell‐division arrest, while transcript reduction supports redistribution of translational machinery. Furthermore, the transient ‘burst’ of mRNA induction after stress serves to accelerate change in the corresponding protein levels. We identified several classes of post‐transcriptional regulation, but show that most of the variance in protein changes is explained by mRNA. Our results present a picture of the coordinated physiological responses at the levels of mRNA, protein, protein‐synthetic capacity, and cellular growth.Keywords
This publication has 71 references indexed in Scilit:
- COMPASS: A suite of pre‐ and post‐search proteomics software tools for OMSSAProteomics, 2011
- Value of Using Multiple Proteases for Large-Scale Mass Spectrometry-Based ProteomicsJournal of Proteome Research, 2010
- Full Dynamic Range Proteome Analysis of S. cerevisiae by Targeted ProteomicsCell, 2009
- A Library of Yeast Transcription Factor Motifs Reveals a Widespread Function for Rsc3 in Targeting Nucleosome Exclusion at PromotersMolecular Cell, 2008
- Single-RNA counting reveals alternative modes of gene expression in yeastNature Structural & Molecular Biology, 2008
- Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeastNature, 2008
- Eukaryotic initiation factor 6 is rate-limiting in translation, growth and transformationNature, 2008
- Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradationMolecular Systems Biology, 2008
- The incoherent feed‐forward loop can generate non‐monotonic input functions for genesMolecular Systems Biology, 2008
- Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noiseNature, 2006