Determinants of efficient modulation of ribosomal traffic jams

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...

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Autores principales:	Sophie Vinokour, Tamir Tuller
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Ribosomal traffic jams Synthetic biology Codon usage mRNA translation Genome evolution Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/92705f4c29cd4ca0a002e72c1ad2e4dd
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spelling	oai:doaj.org-article:92705f4c29cd4ca0a002e72c1ad2e4dd2021-11-20T05:05:23ZDeterminants of efficient modulation of ribosomal traffic jams2001-037010.1016/j.csbj.2021.10.030https://doaj.org/article/92705f4c29cd4ca0a002e72c1ad2e4dd2021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2001037021004529https://doaj.org/toc/2001-0370mRNA 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.Sophie VinokourTamir TullerElsevierarticleRibosomal traffic jamsSynthetic biologyCodon usagemRNA translationGenome evolutionBiotechnologyTP248.13-248.65ENComputational and Structural Biotechnology Journal, Vol 19, Iss , Pp 6064-6079 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ribosomal traffic jams Synthetic biology Codon usage mRNA translation Genome evolution Biotechnology TP248.13-248.65
spellingShingle	Ribosomal traffic jams Synthetic biology Codon usage mRNA translation Genome evolution Biotechnology TP248.13-248.65 Sophie Vinokour Tamir Tuller Determinants of efficient modulation of ribosomal traffic jams
description	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.
format	article
author	Sophie Vinokour Tamir Tuller
author_facet	Sophie Vinokour Tamir Tuller
author_sort	Sophie Vinokour
title	Determinants of efficient modulation of ribosomal traffic jams
title_short	Determinants of efficient modulation of ribosomal traffic jams
title_full	Determinants of efficient modulation of ribosomal traffic jams
title_fullStr	Determinants of efficient modulation of ribosomal traffic jams
title_full_unstemmed	Determinants of efficient modulation of ribosomal traffic jams
title_sort	determinants of efficient modulation of ribosomal traffic jams
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/92705f4c29cd4ca0a002e72c1ad2e4dd
work_keys_str_mv	AT sophievinokour determinantsofefficientmodulationofribosomaltrafficjams AT tamirtuller determinantsofefficientmodulationofribosomaltrafficjams
_version_	1718419610556956672

Determinants of efficient modulation of ribosomal traffic jams

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