Yeast growth is controlled by the proportional scaling of mRNA and ribosome concentrations
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| Format: | Preprint |
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2025
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| _version_ | 1866911113553117184 |
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| author | Gao, Xin Lanz, Michael Grosely, Rosslyn Cremer, Jonas Puglisi, Joseph Skotheim, Jan M. |
| author_facet | Gao, Xin Lanz, Michael Grosely, Rosslyn Cremer, Jonas Puglisi, Joseph Skotheim, Jan M. |
| contents | Despite growth being fundamental to all aspects of cell biology, we do not yet know its organizing principles in eukaryotic cells. Classic models derived from the bacteria E. coli posit that protein-synthesis rates are set by mass-action collisions between charged tRNAs produced by metabolic enzymes and mRNA-bound ribosomes. These models show that faster growth is achieved by simultaneously raising both ribosome content and peptide elongation speed. Here, we test if these models are valid for eukaryotes by combining single-molecule tracking, spike-in RNA sequencing, and proteomics in 15 carbon- and nitrogen-limited conditions using the budding yeast S. cerevisiae. Ribosome concentration increases linearly with growth rate, as in bacteria, but the peptide elongation speed remains constant (~9 amino acids/s) and charged tRNAs are not limiting. Total mRNA concentration rises in direct proportion to ribosomes, driven by enhanced RNA polymerase II occupancy of the genome. We show that a simple kinetic model of mRNA-ribosome binding predicts both the fraction of active ribosomes, the growth rate, and responses to transcriptional perturbations. Yeast accelerate growth by coordinately and proportionally co-up-regulating total mRNA and ribosome concentrations, not by speeding elongation. Taken together, our work establishes a new framework for eukaryotic growth control and resource allocation. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2508_14997 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Yeast growth is controlled by the proportional scaling of mRNA and ribosome concentrations Gao, Xin Lanz, Michael Grosely, Rosslyn Cremer, Jonas Puglisi, Joseph Skotheim, Jan M. Populations and Evolution Biomolecules Despite growth being fundamental to all aspects of cell biology, we do not yet know its organizing principles in eukaryotic cells. Classic models derived from the bacteria E. coli posit that protein-synthesis rates are set by mass-action collisions between charged tRNAs produced by metabolic enzymes and mRNA-bound ribosomes. These models show that faster growth is achieved by simultaneously raising both ribosome content and peptide elongation speed. Here, we test if these models are valid for eukaryotes by combining single-molecule tracking, spike-in RNA sequencing, and proteomics in 15 carbon- and nitrogen-limited conditions using the budding yeast S. cerevisiae. Ribosome concentration increases linearly with growth rate, as in bacteria, but the peptide elongation speed remains constant (~9 amino acids/s) and charged tRNAs are not limiting. Total mRNA concentration rises in direct proportion to ribosomes, driven by enhanced RNA polymerase II occupancy of the genome. We show that a simple kinetic model of mRNA-ribosome binding predicts both the fraction of active ribosomes, the growth rate, and responses to transcriptional perturbations. Yeast accelerate growth by coordinately and proportionally co-up-regulating total mRNA and ribosome concentrations, not by speeding elongation. Taken together, our work establishes a new framework for eukaryotic growth control and resource allocation. |
| title | Yeast growth is controlled by the proportional scaling of mRNA and ribosome concentrations |
| topic | Populations and Evolution Biomolecules |
| url | https://arxiv.org/abs/2508.14997 |