Determinants of efficient modulation of ribosomal traffic jams

Sophie Vinokour, Tamir Tuller

Research output: Contribution to journalArticlepeer-review

Abstract

mRNA translation is the process which consumes most of the cellular energy. Thus, this process is under strong evolutionary selection for its optimization and rational optimization or reduction of the translation efficiency can impact the cell growth rate. Algorithms for modulating cell growth rate can have various applications in biotechnology, medicine, and agriculture. In this study, we demonstrate that the analysis of these algorithms can also be used for understanding translation. We specifically describe and analyze various generic algorithms, based on comprehensive computational models and whole cell simulations of translation, for introducing silent mutations that can either reduce or increase ribosomal traffic jams along the mRNA. As a result, more or less resources are available, for the cell, promoting improved or reduced cells growth-rate, respectively. We then explore the cost of these algorithms' performance, in terms of their computational time, the number of mutations they introduce, the modified genomic region, the effect on local translation rates, and the properties of the modified genes. Among others, we show that mRNA levels of a gene are much stronger predictors for the effect of its engineering on the ribosomal pool than the ribosomal density of the gene. We also demonstrate that the mutations at the ends of the coding regions have a stronger effect on the ribosomal pool. Furthermore, we report two optimization algorithms that exhibit a tread-off between the number of mutations they introduce and their executing time. The reported results here are fundamental both for understanding the biophysics and evolution of translation, as well as for developing efficient approaches for its engineering.

Original languageEnglish
Pages (from-to)6064-6079
Number of pages16
JournalComputational and Structural Biotechnology Journal
Volume19
DOIs
StatePublished - Jan 2021

Keywords

  • Codon usage
  • Genome evolution
  • Ribosomal traffic jams
  • Synthetic biology
  • mRNA translation

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