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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Format: | Article |
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Springer Nature
2013-01-01
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Series: | Molecular Systems Biology |
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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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institution | Directory Open Access Journal |
issn | 1744-4292 |
language | English |
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publishDate | 2013-01-01 |
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series | Molecular Systems Biology |
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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