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The role of codon selection in regulation of translation efficiency deduced from synthetic libraries

BACKGROUND: Translation efficiency is affected by a diversity of parameters, including secondary structure of the transcript and its codon usage. Here we examine the effects of codon usage on translation efficiency by re-analysis of previously constructed synthetic expression libraries in Escherichi...

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Autores principales: Navon, Sivan, Pilpel, Yitzhak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188794/
https://www.ncbi.nlm.nih.gov/pubmed/21284851
http://dx.doi.org/10.1186/gb-2011-12-2-r12
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author Navon, Sivan
Pilpel, Yitzhak
author_facet Navon, Sivan
Pilpel, Yitzhak
author_sort Navon, Sivan
collection PubMed
description BACKGROUND: Translation efficiency is affected by a diversity of parameters, including secondary structure of the transcript and its codon usage. Here we examine the effects of codon usage on translation efficiency by re-analysis of previously constructed synthetic expression libraries in Escherichia coli. RESULTS: We define the region in a gene that takes the longest time to translate as the bottleneck. We found that localization of the bottleneck at the beginning of a transcript promoted a high level of expression, especially if the computed dwell time of the ribosome within this region was sufficiently long. The location and translation time of the bottleneck were not correlated with the cost of expression, approximated by the fitness of the host cell, yet utilization of specific codons was. Particularly, enhanced usage of the codons UCA and CAU was correlated with increased cost of production, potentially due to sequestration of their corresponding rare tRNAs. CONCLUSIONS: The distribution of codons along the genes appears to affect translation efficiency, consistent with analysis of natural genes. This study demonstrates how synthetic biology complements bioinformatics by providing a set-up for well controlled experiments in biology.
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spelling pubmed-31887942011-10-07 The role of codon selection in regulation of translation efficiency deduced from synthetic libraries Navon, Sivan Pilpel, Yitzhak Genome Biol Research BACKGROUND: Translation efficiency is affected by a diversity of parameters, including secondary structure of the transcript and its codon usage. Here we examine the effects of codon usage on translation efficiency by re-analysis of previously constructed synthetic expression libraries in Escherichia coli. RESULTS: We define the region in a gene that takes the longest time to translate as the bottleneck. We found that localization of the bottleneck at the beginning of a transcript promoted a high level of expression, especially if the computed dwell time of the ribosome within this region was sufficiently long. The location and translation time of the bottleneck were not correlated with the cost of expression, approximated by the fitness of the host cell, yet utilization of specific codons was. Particularly, enhanced usage of the codons UCA and CAU was correlated with increased cost of production, potentially due to sequestration of their corresponding rare tRNAs. CONCLUSIONS: The distribution of codons along the genes appears to affect translation efficiency, consistent with analysis of natural genes. This study demonstrates how synthetic biology complements bioinformatics by providing a set-up for well controlled experiments in biology. BioMed Central 2011 2011-02-01 /pmc/articles/PMC3188794/ /pubmed/21284851 http://dx.doi.org/10.1186/gb-2011-12-2-r12 Text en Copyright ©2011 Navon and Pilpel; licensee BioMed Central Ltd. http://(http://creativecommons.org/licenses/by/2.0) This is an open access article distributed under the terms of the Creative Commons Attribution License http://(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Navon, Sivan
Pilpel, Yitzhak
The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title_full The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title_fullStr The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title_full_unstemmed The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title_short The role of codon selection in regulation of translation efficiency deduced from synthetic libraries
title_sort role of codon selection in regulation of translation efficiency deduced from synthetic libraries
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188794/
https://www.ncbi.nlm.nih.gov/pubmed/21284851
http://dx.doi.org/10.1186/gb-2011-12-2-r12
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