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Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis

Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein s...

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Autores principales: Meng, Xiang, Firczuk, Helena, Pietroni, Paola, Westbrook, Richard, Dacheux, Estelle, Mendes, Pedro, McCarthy, John E.G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314777/
https://www.ncbi.nlm.nih.gov/pubmed/27928055
http://dx.doi.org/10.1093/nar/gkw1194
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author Meng, Xiang
Firczuk, Helena
Pietroni, Paola
Westbrook, Richard
Dacheux, Estelle
Mendes, Pedro
McCarthy, John E.G.
author_facet Meng, Xiang
Firczuk, Helena
Pietroni, Paola
Westbrook, Richard
Dacheux, Estelle
Mendes, Pedro
McCarthy, John E.G.
author_sort Meng, Xiang
collection PubMed
description Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point.
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spelling pubmed-53147772017-02-21 Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis Meng, Xiang Firczuk, Helena Pietroni, Paola Westbrook, Richard Dacheux, Estelle Mendes, Pedro McCarthy, John E.G. Nucleic Acids Res Synthetic Biology and Bioengineering Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point. Oxford University Press 2017-01-25 2016-12-07 /pmc/articles/PMC5314777/ /pubmed/27928055 http://dx.doi.org/10.1093/nar/gkw1194 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Synthetic Biology and Bioengineering
Meng, Xiang
Firczuk, Helena
Pietroni, Paola
Westbrook, Richard
Dacheux, Estelle
Mendes, Pedro
McCarthy, John E.G.
Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title_full Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title_fullStr Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title_full_unstemmed Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title_short Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis
title_sort minimum-noise production of translation factor eif4g maps to a mechanistically determined optimal rate control window for protein synthesis
topic Synthetic Biology and Bioengineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314777/
https://www.ncbi.nlm.nih.gov/pubmed/27928055
http://dx.doi.org/10.1093/nar/gkw1194
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