Yeast growth is controlled by the proportional scaling of mRNA and ribosome concentrations

TL;DR

This study reveals that yeast growth is regulated by proportional increases in mRNA and ribosome concentrations, rather than by faster peptide elongation, challenging existing bacterial models and proposing a new eukaryotic growth framework.

Contribution

It demonstrates that yeast growth control involves proportional scaling of mRNA and ribosomes, not changes in elongation speed, supported by comprehensive multi-omics data and a kinetic binding model.

Findings

Ribosome concentration increases linearly with growth rate.

Peptide elongation speed remains constant (~9 amino acids/sec).

Total mRNA scales proportionally with ribosome levels.

Abstract

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.