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Translation elongation and mRNA stability are coupled through the ribosomal A-site

Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that opt...

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Autores principales: Hanson, Gavin, Alhusaini, Najwa, Morris, Nathan, Sweet, Thomas, Coller, Jeff
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140462/
https://www.ncbi.nlm.nih.gov/pubmed/29997263
http://dx.doi.org/10.1261/rna.066787.118
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author Hanson, Gavin
Alhusaini, Najwa
Morris, Nathan
Sweet, Thomas
Coller, Jeff
author_facet Hanson, Gavin
Alhusaini, Najwa
Morris, Nathan
Sweet, Thomas
Coller, Jeff
author_sort Hanson, Gavin
collection PubMed
description Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increases mRNA stability. However, a direct relationship between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wild-type yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11 HIS3 reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast.
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spelling pubmed-61404622019-10-01 Translation elongation and mRNA stability are coupled through the ribosomal A-site Hanson, Gavin Alhusaini, Najwa Morris, Nathan Sweet, Thomas Coller, Jeff RNA Article Messenger RNA (mRNA) degradation plays a critical role in regulating transcript levels in eukaryotic cells. Previous work by us and others has shown that codon identity exerts a powerful influence on mRNA stability. In Saccharomyces cerevisiae, studies using a handful of reporter mRNAs show that optimal codons increase translation elongation rate, which in turn increases mRNA stability. However, a direct relationship between elongation rate and mRNA stability has not been established across the entire yeast transcriptome. In addition, there is evidence from work in higher eukaryotes that amino acid identity influences mRNA stability, raising the question as to whether the impact of translation elongation on mRNA decay is at the level of tRNA decoding, amino acid incorporation, or some combination of each. To address these questions, we performed ribosome profiling of wild-type yeast. In good agreement with other studies, our data showed faster codon-specific elongation over optimal codons and faster transcript-level elongation correlating with transcript optimality. At both the codon-level and transcript-level, faster elongation correlated with increased mRNA stability. These findings were reinforced by showing increased translation efficiency and kinetics for a panel of 11 HIS3 reporter mRNAs of increasing codon optimality. While we did observe that elongation measured by ribosome profiling is composed of both amino acid identity and synonymous codon effects, further analyses of these data establish that A-site tRNA decoding rather than other steps of translation elongation is driving mRNA decay in yeast. Cold Spring Harbor Laboratory Press 2018-10 /pmc/articles/PMC6140462/ /pubmed/29997263 http://dx.doi.org/10.1261/rna.066787.118 Text en © 2018 Hanson et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Hanson, Gavin
Alhusaini, Najwa
Morris, Nathan
Sweet, Thomas
Coller, Jeff
Translation elongation and mRNA stability are coupled through the ribosomal A-site
title Translation elongation and mRNA stability are coupled through the ribosomal A-site
title_full Translation elongation and mRNA stability are coupled through the ribosomal A-site
title_fullStr Translation elongation and mRNA stability are coupled through the ribosomal A-site
title_full_unstemmed Translation elongation and mRNA stability are coupled through the ribosomal A-site
title_short Translation elongation and mRNA stability are coupled through the ribosomal A-site
title_sort translation elongation and mrna stability are coupled through the ribosomal a-site
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140462/
https://www.ncbi.nlm.nih.gov/pubmed/29997263
http://dx.doi.org/10.1261/rna.066787.118
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