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Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation

The codon stabilization coefficient (CSC) is derived from the correlation between each codon frequency in transcripts and mRNA half-life experimental data. In this work, we used this metric as a reference to compare previously published Saccharomyces cerevisiae mRNA half-life datasets and investigat...

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Autores principales: Carneiro, Rodolfo L, Requião, Rodrigo D, Rossetto, Silvana, Domitrovic, Tatiana, Palhano, Fernando L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412131/
https://www.ncbi.nlm.nih.gov/pubmed/30698781
http://dx.doi.org/10.1093/nar/gkz033
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author Carneiro, Rodolfo L
Requião, Rodrigo D
Rossetto, Silvana
Domitrovic, Tatiana
Palhano, Fernando L
author_facet Carneiro, Rodolfo L
Requião, Rodrigo D
Rossetto, Silvana
Domitrovic, Tatiana
Palhano, Fernando L
author_sort Carneiro, Rodolfo L
collection PubMed
description The codon stabilization coefficient (CSC) is derived from the correlation between each codon frequency in transcripts and mRNA half-life experimental data. In this work, we used this metric as a reference to compare previously published Saccharomyces cerevisiae mRNA half-life datasets and investigate how codon composition related to protein levels. We generated CSCs derived from nine studies. Four datasets produced similar CSCs, which also correlated with other independent parameters that reflected codon optimality, such as the tRNA abundance and ribosome residence time. By calculating the average CSC for each gene, we found that most mRNAs tended to have more non-optimal codons. Conversely, a high proportion of optimal codons was found for genes coding highly abundant proteins, including proteins that were only transiently overexpressed in response to stress conditions. We also used CSCs to identify and locate mRNA regions enriched in non-optimal codons. We found that these stretches were usually located close to the initiation codon and were sufficient to slow ribosome movement. However, in contrast to observations from reporter systems, we found no position-dependent effect on the mRNA half-life. These analyses underscore the value of CSCs in studies of mRNA stability and codon bias and their relationships with protein expression.
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spelling pubmed-64121312019-03-18 Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation Carneiro, Rodolfo L Requião, Rodrigo D Rossetto, Silvana Domitrovic, Tatiana Palhano, Fernando L Nucleic Acids Res Computational Biology The codon stabilization coefficient (CSC) is derived from the correlation between each codon frequency in transcripts and mRNA half-life experimental data. In this work, we used this metric as a reference to compare previously published Saccharomyces cerevisiae mRNA half-life datasets and investigate how codon composition related to protein levels. We generated CSCs derived from nine studies. Four datasets produced similar CSCs, which also correlated with other independent parameters that reflected codon optimality, such as the tRNA abundance and ribosome residence time. By calculating the average CSC for each gene, we found that most mRNAs tended to have more non-optimal codons. Conversely, a high proportion of optimal codons was found for genes coding highly abundant proteins, including proteins that were only transiently overexpressed in response to stress conditions. We also used CSCs to identify and locate mRNA regions enriched in non-optimal codons. We found that these stretches were usually located close to the initiation codon and were sufficient to slow ribosome movement. However, in contrast to observations from reporter systems, we found no position-dependent effect on the mRNA half-life. These analyses underscore the value of CSCs in studies of mRNA stability and codon bias and their relationships with protein expression. Oxford University Press 2019-03-18 2019-01-30 /pmc/articles/PMC6412131/ /pubmed/30698781 http://dx.doi.org/10.1093/nar/gkz033 Text en © The Author(s) 2019. 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 Computational Biology
Carneiro, Rodolfo L
Requião, Rodrigo D
Rossetto, Silvana
Domitrovic, Tatiana
Palhano, Fernando L
Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title_full Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title_fullStr Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title_full_unstemmed Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title_short Codon stabilization coefficient as a metric to gain insights into mRNA stability and codon bias and their relationships with translation
title_sort codon stabilization coefficient as a metric to gain insights into mrna stability and codon bias and their relationships with translation
topic Computational Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412131/
https://www.ncbi.nlm.nih.gov/pubmed/30698781
http://dx.doi.org/10.1093/nar/gkz033
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