title: One third of dynamic protein expression profiles can be predicted by a simple rate equation.
abstract: Cells respond to environmental stimuli with expression changes at both the mRNA and protein level, and a plethora of known and unknown regulators affect synthesis and degradation rates of the resulting proteins. To investigate the major principles of gene expression regulation in dynamic systems, we estimated protein synthesis and degradation rates from parallel time series data of mRNA and protein expression and tested the degree to which expression changes can be modeled by a simple linear differential equation. Examining three published datasets for yeast responding to diamide, rapamycin, and sodium chloride treatment, we find that almost one-third of genes can be well-modeled, and the estimated rates assume realistic values. Prediction quality is linked to low measurement noise and the shape of the expression profile. Synthesis and degradation rates do not correlate within one treatment, consistent with their independent regulation. When performing robustness analyses of the rate estimates, we observed that most genes adhere to one of two major modes of regulation, which we term synthesis- and degradation-independent regulation. These two modes, in which only one of the rates has to be tightly set, while the other one can assume various values, offer an efficient way for the cell to respond to stimuli and re-establish proteostasis. We experimentally validate degradation-independent regulation under oxidative stress for the heatshock protein Ssa4.
authors.affiliation: Center for Genomics and Systems Biology, New York University, New York, USA. cvogel@nyu.edu.
authors.forename: Konstantine
authors.initials: K
authors.lastname: Tchourine
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Poultney
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Gustavo M
authors.initials: GM
authors.lastname: Silva
authors.forename: Sandhya
authors.initials: S
authors.lastname: Manohar
authors.forename: Christian L
authors.initials: CL
authors.lastname: Mueller
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.forename: Christine
authors.initials: C
authors.lastname: Vogel
mesh_terms: D000465:Algorithms; D003958:Diamide / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D008957:Models, Genetic; D018384:Oxidative Stress; D059748:Proteolysis; D020123:Sirolimus / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D015003:Yeasts / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D003958:Diamide; D012965:Sodium Chloride; D020123:Sirolimus
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