Translation in the cell under fierce competition for shared resources: a mathematical model

Rami Katz, Elad Attias, Tamir Tuller, Michael Margaliot

Research output: Contribution to journalArticlepeer-review

Abstract

During translation, mRNAs 'compete' for shared resources. Under stress conditions, during viral infection and also in high-throughput heterologous gene expression, these resources may become scarce, e.g. the pool of free ribosomes is starved, and then the competition may have a dramatic effect on the global dynamics of translation in the cell. We model this scenario using a network that includes m ribosome flow models (RFMs) interconnected via a pool of free ribosomes. Each RFM models ribosome flow along an mRNA molecule, and the pool models the shared resource. We assume that the number of mRNAs is large, so many ribosomes are attached to the mRNAs, and the pool is starved. Our analysis shows that adding an mRNA has an intricate effect on the total protein production. The new mRNA produces new proteins, but the other mRNAs produce less proteins, as the pool that feeds these mRNAs now has a smaller abundance of ribosomes. As the number of mRNAs increases, the marginal utility of adding another mRNA diminishes, and the total protein production rate saturates to a limiting value. We demonstrate our approach using an example of insulin protein production in a cell-free system.

Original languageEnglish
Pages (from-to)20220535
Number of pages1
JournalJournal of the Royal Society Interface
Volume19
Issue number197
DOIs
StatePublished - 1 Dec 2022

Keywords

  • cell-free systems
  • competition for shared resources
  • mRNA translation
  • Perron–Frobenius theory
  • perturbations of eigenvalues and eigenvectors
  • spectral analysis of tri-diagonal matrices

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