An in vivo control map for the eukaryotic mRNA translation machinery

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non‐intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non‐stoichi...

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Main Authors: Helena Firczuk, Shichina Kannambath, Jürgen Pahle, Amy Claydon, Robert Beynon, John Duncan, Hans Westerhoff, Pedro Mendes, John EG McCarthy
Format: Article
Language:English
Published: Springer Nature 2013-01-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/msb.2012.73
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author Helena Firczuk
Shichina Kannambath
Jürgen Pahle
Amy Claydon
Robert Beynon
John Duncan
Hans Westerhoff
Pedro Mendes
John EG McCarthy
author_facet Helena Firczuk
Shichina Kannambath
Jürgen Pahle
Amy Claydon
Robert Beynon
John Duncan
Hans Westerhoff
Pedro Mendes
John EG McCarthy
author_sort Helena Firczuk
collection DOAJ
description Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non‐intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non‐stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than‐average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.
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spelling doaj.art-21360f3ab49f404c94447d22b8b899b62024-03-03T09:32:04ZengSpringer NatureMolecular Systems Biology1744-42922013-01-0191n/an/a10.1038/msb.2012.73An in vivo control map for the eukaryotic mRNA translation machineryHelena Firczuk0Shichina Kannambath1Jürgen Pahle2Amy Claydon3Robert Beynon4John Duncan5Hans Westerhoff6Pedro Mendes7John EG McCarthy8School of Life Sciences, University of Warwick Coventry UKSchool of Life Sciences, University of Warwick Coventry UKManchester Interdisciplinary Biocentre, University of Manchester Manchester UKInstitute of Integrative Biology, University of Liverpool Liverpool UKInstitute of Integrative Biology, University of Liverpool Liverpool UKSchool of Life Sciences, University of Warwick Coventry UKManchester Interdisciplinary Biocentre, University of Manchester Manchester UKManchester Interdisciplinary Biocentre, University of Manchester Manchester UKSchool of Life Sciences, University of Warwick Coventry UKRate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non‐intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non‐stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNAi to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than‐average 5′untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5′UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.https://doi.org/10.1038/msb.2012.73eukaryotic translation machinerygene duplicationin vivo rate controlpost‐transcriptional gene expressionsystem modularity
spellingShingle Helena Firczuk
Shichina Kannambath
Jürgen Pahle
Amy Claydon
Robert Beynon
John Duncan
Hans Westerhoff
Pedro Mendes
John EG McCarthy
An in vivo control map for the eukaryotic mRNA translation machinery
Molecular Systems Biology
eukaryotic translation machinery
gene duplication
in vivo rate control
post‐transcriptional gene expression
system modularity
title An in vivo control map for the eukaryotic mRNA translation machinery
title_full An in vivo control map for the eukaryotic mRNA translation machinery
title_fullStr An in vivo control map for the eukaryotic mRNA translation machinery
title_full_unstemmed An in vivo control map for the eukaryotic mRNA translation machinery
title_short An in vivo control map for the eukaryotic mRNA translation machinery
title_sort in vivo control map for the eukaryotic mrna translation machinery
topic eukaryotic translation machinery
gene duplication
in vivo rate control
post‐transcriptional gene expression
system modularity
url https://doi.org/10.1038/msb.2012.73
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