Translational efficiency across healthy and tumor tissues is proliferation‐related

Abstract Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon–anticodon co‐adaptation in humans is not completely understood, nor is its effect on tissue‐specific protein levels. Here, we first validated the accuracy of small RNA‐seq for tRNA...

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Main Authors: Xavier Hernandez‐Alias, Hannah Benisty, Martin H Schaefer, Luis Serrano
Format: Article
Language:English
Published: Springer Nature 2020-03-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.15252/msb.20199275
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author Xavier Hernandez‐Alias
Hannah Benisty
Martin H Schaefer
Luis Serrano
author_facet Xavier Hernandez‐Alias
Hannah Benisty
Martin H Schaefer
Luis Serrano
author_sort Xavier Hernandez‐Alias
collection DOAJ
description Abstract Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon–anticodon co‐adaptation in humans is not completely understood, nor is its effect on tissue‐specific protein levels. Here, we first validated the accuracy of small RNA‐seq for tRNA quantification across five human cell lines. We then analyzed the tRNA abundance of more than 8,000 tumor samples from TCGA, together with their paired mRNA‐seq and proteomics data, to determine the Supply‐to‐Demand Adaptation. We thereby elucidate that the dynamic adaptation of the tRNA pool is largely related to the proliferative state across tissues. The distribution of such tRNA pools over the whole cellular translatome affects the subsequent translational efficiency, which functionally determines a condition‐specific expression program both in healthy and tumor states. Furthermore, the aberrant translational efficiency of some codons in cancer, exemplified by ArgAGA, is associated with poor patient survival†. The regulation of these tRNA profiles is partly explained by the tRNA gene copy numbers and their promoter DNA methylation.
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spelling doaj.art-5328167fdb934cf4bd1d3f8b3a425a362024-03-02T13:36:04ZengSpringer NatureMolecular Systems Biology1744-42922020-03-01163n/an/a10.15252/msb.20199275Translational efficiency across healthy and tumor tissues is proliferation‐relatedXavier Hernandez‐Alias0Hannah Benisty1Martin H Schaefer2Luis Serrano3Centre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology Barcelona SpainCentre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology Barcelona SpainCentre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology Barcelona SpainCentre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology Barcelona SpainAbstract Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon–anticodon co‐adaptation in humans is not completely understood, nor is its effect on tissue‐specific protein levels. Here, we first validated the accuracy of small RNA‐seq for tRNA quantification across five human cell lines. We then analyzed the tRNA abundance of more than 8,000 tumor samples from TCGA, together with their paired mRNA‐seq and proteomics data, to determine the Supply‐to‐Demand Adaptation. We thereby elucidate that the dynamic adaptation of the tRNA pool is largely related to the proliferative state across tissues. The distribution of such tRNA pools over the whole cellular translatome affects the subsequent translational efficiency, which functionally determines a condition‐specific expression program both in healthy and tumor states. Furthermore, the aberrant translational efficiency of some codons in cancer, exemplified by ArgAGA, is associated with poor patient survival†. The regulation of these tRNA profiles is partly explained by the tRNA gene copy numbers and their promoter DNA methylation.https://doi.org/10.15252/msb.20199275codon usageThe Cancer Genome AtlastissuetranslationtRNA
spellingShingle Xavier Hernandez‐Alias
Hannah Benisty
Martin H Schaefer
Luis Serrano
Translational efficiency across healthy and tumor tissues is proliferation‐related
Molecular Systems Biology
codon usage
The Cancer Genome Atlas
tissue
translation
tRNA
title Translational efficiency across healthy and tumor tissues is proliferation‐related
title_full Translational efficiency across healthy and tumor tissues is proliferation‐related
title_fullStr Translational efficiency across healthy and tumor tissues is proliferation‐related
title_full_unstemmed Translational efficiency across healthy and tumor tissues is proliferation‐related
title_short Translational efficiency across healthy and tumor tissues is proliferation‐related
title_sort translational efficiency across healthy and tumor tissues is proliferation related
topic codon usage
The Cancer Genome Atlas
tissue
translation
tRNA
url https://doi.org/10.15252/msb.20199275
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AT hannahbenisty translationalefficiencyacrosshealthyandtumortissuesisproliferationrelated
AT martinhschaefer translationalefficiencyacrosshealthyandtumortissuesisproliferationrelated
AT luisserrano translationalefficiencyacrosshealthyandtumortissuesisproliferationrelated