scholarly journals Principles of cellular resource allocation revealed by condition-dependent proteome profiling

2017 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Ilya Soifer ◽  
Yonat Gurvich ◽  
...  

Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of other proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce an excess of ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells do not contribute to translation. This fraction increases as growth rate decreases. These excess ribosomal proteins are employed during nutrient upshift or when forcing unneeded expression. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Eyal Metzl-Raz ◽  
Moshe Kafri ◽  
Gilad Yaakov ◽  
Ilya Soifer ◽  
Yonat Gurvich ◽  
...  

Growing cells coordinate protein translation with metabolic rates. Central to this coordination is ribosome production. Ribosomes drive cell growth, but translation of ribosomal proteins competes with production of non-ribosomal proteins. Theory shows that cell growth is maximized when all expressed ribosomes are constantly translating. To examine whether budding yeast function at this limit of full ribosomal usage, we profiled the proteomes of cells growing in different environments. We find that cells produce excess ribosomal proteins, amounting to a constant ≈8% of the proteome. Accordingly, ≈25% of ribosomal proteins expressed in rapidly growing cells does not contribute to translation. Further, this fraction increases as growth rate decreases and these excess ribosomal proteins are employed when translation demands unexpectedly increase. We suggest that steadily growing cells prepare for conditions that demand increased translation by producing excess ribosomes, at the expense of lower steady-state growth rate.


2016 ◽  
Vol 27 (8) ◽  
pp. 1383-1396 ◽  
Author(s):  
Edoardo M. Airoldi ◽  
Darach Miller ◽  
Rodoniki Athanasiadou ◽  
Nathan Brandt ◽  
Farah Abdul-Rahman ◽  
...  

Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR-regulated permease genes GAP1, MEP2, DAL5, PUT4, and DIP5. Our results reveal novel aspects of nitrogen-regulated gene expression and highlight the need for a quantitative approach to study how the cell coordinates protein translation and nitrogen assimilation to optimize cell growth in different environments.


1975 ◽  
Vol 150 (3) ◽  
pp. 469-475 ◽  
Author(s):  
H Bremer ◽  
P P Dennis

The relative transcriptional activities of genes coding for ribosomal RNA (rRNA) and ribosomal proteins (r-proteins) at a steady-state growth rates ranging from 0.65 to 2.1 doublings/h can be estimated from previous measurements of the synthesis rates of stable and unstable RNA (Pato & von Meyenburg, 1970; Nierlich, 1972a,b; Bremer et al., 1973; Dennis & Bremer, 1973b, 1974b) and ribosomal proteins (Schleif, 1967; Dennis & Bremer, 1974a). Comparison of these transcriptional activities suggests that the expression of the r-protein genes and rRNA genes is controlled seperately.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Samuel Frederick Mock Hart ◽  
Jose Mario Bello Pineda ◽  
Chi-Chun Chen ◽  
Robin Green ◽  
Wenying Shou

Mutualisms can be promoted by pleiotropic win-win mutations which directly benefit self (self-serving) and partner (partner-serving). Intuitively, partner-serving phenotype could be quantified as an individual’s benefit supply rate to partners. Here, we demonstrate the inadequacy of this thinking, and propose an alternative. Specifically, we evolved well-mixed mutualistic communities where two engineered yeast strains exchanged essential metabolites lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, a chromosome duplication mutation seemed win-win: it improved cell’s affinity for lysine (self-serving), and increased hypoxanthine release rate per cell (partner-serving). However, increased release rate was due to increased cell size accompanied by increased lysine utilization per birth. Consequently, total hypoxanthine release rate per lysine utilization (defined as ‘exchange ratio’) remained unchanged. Indeed, this mutation did not increase the steady state growth rate of partner, and is thus solely self-serving during long-term growth. By extension, reduced benefit production rate by an individual may not imply cheating.


2021 ◽  
Author(s):  
Yufei Wu ◽  
Paul Janmey ◽  
Sean X. Sun

In eukaryotes, the cell volume is observed to be strongly correlated with the nuclear volume. The slope of this correlation depends on the cell type, growth condition, and the physical environment of the cell. We develop a computational model of cell growth and proteome increase, incorporating the kinetics of amino acid import, protein/ribosome synthesis and degradation, and active transport of proteins between the cytoplasm and the nucleoplasm. We also include a simple model of ribosome biogenesis and assembly. Results show that the cell volume is tightly correlated with the nuclear volume, and the cytoplasm-nucleoplasm transport rates strongly influences the cell growth rate as well as the cytoplasm/nucleoplasm ratio. Ribosome assembly and the ratio of ribosomal proteins to mature ribosomes also influence the cell volume and the cell growth rate. We find that in order to regulate the cell growth rate and the cytoplasm/nucleoplasm ratio, the cell must optimally control groups of kinetic parameters together, which could explain the quantitative roles of canonical growth pathways. Finally, using an extension of our model and single cell RNAseq data, it is possible to construct a detailed proteome distribution, provided that a cell division mechanism is known.


Author(s):  
Rup Singh

This chapter is a brief account of what we now observe in the growth literature in light of the developments in the voluminous empirical works on economic growth. It is argued that while the empirical knowledge has advanced adequately, little progress has been made in the growth theory since the classic works of Solow. Therefore it can be said that growth economist and policy makers are still confused on how to raise the steady state growth rate of output and some of these confusions are due to our own experiments.


1999 ◽  
Vol 3 (4) ◽  
pp. 482-505 ◽  
Author(s):  
Satyajit Chatterjee ◽  
B. Ravikumar

We study the impact of a minimum consumption requirement on the rate of economic growth and the evolution of wealth distribution. The requirement introduces a positive dependence between the intertemporal elasticity of substitution and household wealth. This dependence implies a transition phase during which the growth rate of per-capita quantities rise toward their steady-state values and the distributions of wealth, consumption, and permanent income become more unequal. We calibrate the minimum consumption requirement to match estimates available for a sample of Indian villagers and find that these transitional effects are quantitatively significant and depend importantly on the economy's steady-state growth rate.


2021 ◽  
Vol 9 (59) ◽  

This study aims to estimate the steady-state growth rate or the natural growth rate and to determine whether the steady-state growth rate is endogenous to demand conditions or not. In order to achieve these aims, this study makes an econometric analysis using ordinary least squares method based on the data of Turkey covering the period 1969-2006. The present study estimates the natural growth rate and analyzes whether the natural growth rate is endogenous or not. But, different from the previous studies, the present study makes estimations in the conditions that capital-output ratio remains constant. According to the results of the study, the steady-state or natural growth rate is 5.71% in Turkey for the period 1969-2006. Moreover, the natural growth rate becomes 9.51% in the boom periods. This result shows that the steady-state or natural growth rate is endogenous to demand conditions in Turkey. Thus, the present study provides evidence for the Thirlwall’s (1969) theory in a different manner. Keywords: Natural growth rate, endogeneity, steady-state, capital-output ratio, economic history of Turkey


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