Slowing translation to avoid ribosome population extinction and maintain stable allocation at slow growth rates

Dotan Goberman; Anjan Roy; Rami Pugatch

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arXiv · 2503.07837

Slowing translation to avoid ribosome population extinction and maintain stable allocation at slow growth rates

Dotan Goberman·Anjan Roy·Rami Pugatch

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Abstract

To double the cellular population of ribosomes, a fraction of the active ribosomes is allocated to synthesize ribosomal proteins. Subsequently, these ribosomal proteins enter the ribosome self-assembly process, synthesizing new ribosomes and forming the well-known ribosome autocatalytic subcycle. Neglecting ribosome lifetime and the duration of the self-assembly process, the doubling rate of all cellular biomass can be equated with the fraction of ribosomes allocated to synthesize an essential ribosomal protein times its synthesis rate. However, ribosomes have a finite lifetime, and the assembly process has a finite duration. Furthermore, the number of ribosomes is known to decrease with slow growth rates. The finite lifetime of ribosomes and the decline in their numbers present a challenge in sustaining slow growth solely through controlling the allocation of ribosomes to synthesize more ribosomal proteins. When the number of ribosomes allocated per mRNA of an essential ribosomal protein is approximately one, the resulting fluctuations in the production rate of new ribosomes increase, causing a potential risk that the actual production rate will fall below the ribosome death rate. Thus, in this regime, a significant risk of extinction of the ribosome population emerges. To mitigate this risk, we suggest that the ribosome translation speed is used as an alternative control parameter, which facilitates the maintenance of slow growth rates with a larger ribosome pool. We clarify the observed reduction in translation speed at harsh environments in E. coli and C. Glutamicum, explore other mitigation strategies, and suggest additional falsifiable predictions of our model.

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Dotan Goberman, Anjan Roy, Rami Pugatch. 2025-03-10. Slowing translation to avoid ribosome population extinction and maintain stable allocation at slow growth rates. https://arxiv.org/abs/2503.07837

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