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Differential Scaling of Gene Expression with Cell Size May Explain Size Control in Budding Yeast.

ABSTRACT: Yeast cells must grow to a critical size before committing to division. It is unknown how size is measured. We find that as cells grow, mRNAs for some cell-cycle activators scale faster than size, increasing in concentration, while mRNAs for some inhibitors scale slower than size, decreasing in concentration. Size-scaled gene expression could cause an increasing ratio of activators to inhibitors with size, triggering cell-cycle entry. Consistent with this, expression of the CLN2 activator from the promoter of the WHI5 inhibitor, or vice versa, interfered with cell size homeostasis, yielding a broader distribution of cell sizes. We suggest that size homeostasis comes from differential scaling of gene expression with size. Differential regulation of gene expression as a function of cell size could affect many cellular processes.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7963363 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Differential scaling of gene expression with cell size may explain size control in budding yeast.

Project description:Yeast cells must grow to a critical size before committing to division. It is unknown how size is measured. We find that as cells grow, mRNAs for some cell cycle activators scale faster than size, increasing in concentration, while mRNAs for some inhibitors scale slower than size, decreasing in concentration. Size-scaled gene expression could cause an increasing ratio of activators to inhibitors with size, triggering cell cycle entry. Consistent with this, expression of the CLN2 activator from the promoter of the WHI5 inhibitor, or vice versa, interfered with cell size homeostasis, yielding a broader distribution of cell sizes. We suggest that size homeostasis comes from differential scaling of gene expression with size. Such regulation of gene expression as a function of cell size could affect many cellular processes.

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Differential scaling of gene expression with cell size may explain size control in budding yeast.

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Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast

Project description:In the unicellular eukaryote Saccharomyces cerevisiae, Cln3-CDK activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in protein production rate, which do not scale with cell size dynamics, but -following the intrinsic metabolic dynamics- peak around Start. Using a viral-based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population level, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells, across growth conditions. Thus, uncoupling between two fundamental physiological parameters drives cell cycle commitment.

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Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast

Project description:In the unicellular eukaryote Saccharomyces cerevisiae, Cln3–cyclin-dependent kinase activity enables Start, the irreversible commitment to the cell division cycle. However, the concentration of Cln3 has been paradoxically considered to remain constant during G1, due to the presumed scaling of its production rate with cell size dynamics. Measuring metabolic and biosynthetic activity during cell cycle progression in single cells, we found that cells exhibit pulses in their protein production rate. Rather than scaling with cell size dynamics, these pulses follow the intrinsic metabolic dynamics, peaking around Start. Using a viral- based bicistronic construct and targeted proteomics to measure Cln3 at the single-cell and population levels, we show that the differential scaling between protein production and cell size leads to a temporal increase in Cln3 concentration, and passage through Start. This differential scaling causes Start in both daughter and mother cells across growth conditions. Thus, uncou- pling between two fundamental physiological parameters drives cell cycle commitment.

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