Abstract
Cellular resources are limited and their relative allocation to gene expression programmes determines physiological states and global properties such as the growth rate. Here, we determined the importance of the growth rate in explaining relative changes in protein and mRNA levels in the simple eukaryote Schizosaccharomyces pombe grown on non-limiting nitrogen sources. Although expression of half of fission yeast genes was significantly correlated with the growth rate, this came alongside wide-spread nutrient-specific regulation. Proteome and transcriptome often showed coordinated regulation but with notable exceptions, such as metabolic enzymes. Genes positively correlated with growth rate participated in every level of protein production apart from RNA polymerase II-dependent transcription. Negatively correlated genes belonged mainly to the environmental stress response programme. Critically, metabolic enzymes, which represent ∼55-70% of the proteome by mass, showed mostly condition-specific regulation. In summary, we provide a rich account of resource allocation to gene expression in a simple eukaryote, advancing our basic understanding of the interplay between growth-rate-dependent and nutrient-specific gene expression.
Highlights
Cellular growth is the process by which cells increase in mass
To generate cell populations that grow at different rates but not limited for nutrients, we used eight defined culture media, each containing a unique source of nitrogen
Of all the genes detected in the proteome across the eight conditions examined, we found that 22% of proteins and 37% of mRNA belonged to the R-sector; 24% and 21% of the proteins and mRNA
Summary
Cellular growth is the process by which cells increase in mass. It is a fundamental systemic process that impacts most aspects of cell physiology. For cultures undergoing balanced exponential growth modulated by external nutrients, the total RNA abundance per unit of biomass and the growth rate are correlated linearly This phenomenological relationship is called the first or ribosomal growth law and reflects an increased requirement for ribosomes during faster growth to support protein synthesis. It was shown that about half of the total protein mass in Escherichia coli responded to growth modulations by nutrient limitation and translational inhibition (Scott et al, 2010; You et al, 2013) These observations were formalised in a phenomenological model separating the proteome into three broad sectors based on their growth rate correlations. Proteins showing expression levels positively correlated with the cellular growth rate during nutrient limitation and negatively during translational inhibition form the R-sector (as many of them are constituents of the ribosome). The concept of proteome sectors has been the basis of several phenomenological and coarse-grained mechanistic models relating optimal resource allocation to protein abundance and cellular growth rates (Molenaar et al, 2009; Scott et al, 2014; Maitra & Dill, 2015; Weiße et al, 2015; Pandey & Jain, 2016; Liao et al, 2017; Bertaux et al, 2020; Hu et al, 2020)
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