Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues
Abstract Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein‐to‐mRNA (PTR) ratios and a quantification of their effects are still lacking. Here, we quantified PTR ratios for 11,575 proteins across 29 human tissues using matche...
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doaj-e19bbe0271ae4aadb03af672401fd3572021-08-02T22:30:40ZengWileyMolecular Systems Biology1744-42922019-02-01152n/an/a10.15252/msb.20188513Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissuesBasak Eraslan0Dongxue Wang1Mirjana Gusic2Holger Prokisch3Björn M Hallström4Mathias Uhlén5Anna Asplund6Frederik Pontén7Thomas Wieland8Thomas Hopf9Hannes Hahne10Bernhard Kuster11Julien Gagneur12Computational Biology Department of Informatics Technical University of Munich Garching Munich GermanyChair of Proteomics and Bioanalytics Technical University of Munich Freising GermanyInstitute of Human Genetics Technical University of Munich Munich GermanyInstitute of Human Genetics Technical University of Munich Munich GermanyScience for Life Laboratory KTH ‐ Royal Institute of Technology Stockholm SwedenScience for Life Laboratory KTH ‐ Royal Institute of Technology Stockholm SwedenDepartment of Immunology, Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala SwedenDepartment of Immunology, Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala SwedenChair of Proteomics and Bioanalytics Technical University of Munich Freising GermanyChair of Proteomics and Bioanalytics Technical University of Munich Freising GermanyOmicScouts GmbH Freising GermanyChair of Proteomics and Bioanalytics Technical University of Munich Freising GermanyComputational Biology Department of Informatics Technical University of Munich Garching Munich GermanyAbstract Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein‐to‐mRNA (PTR) ratios and a quantification of their effects are still lacking. Here, we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We estimated by regression the contribution of known sequence determinants of protein synthesis and degradation in addition to 45 mRNA and 3 protein sequence motifs that we found by association testing. While PTR ratios span more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2‐fold. A reporter assay provided functional support for two novel UTR motifs, and an immobilized mRNA affinity competition‐binding assay identified motif‐specific bound proteins for one motif. Moreover, our integrative model led to a new metric of codon optimality that captures the effects of codon frequency on protein synthesis and degradation. Altogether, this study shows that a large fraction of PTR ratio variation in human tissues can be predicted from sequence, and it identifies many new candidate post‐transcriptional regulatory elements.https://doi.org/10.15252/msb.20188513codon usagemRNA sequence motifsproteomicstranscriptomicstranslational control |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Basak Eraslan Dongxue Wang Mirjana Gusic Holger Prokisch Björn M Hallström Mathias Uhlén Anna Asplund Frederik Pontén Thomas Wieland Thomas Hopf Hannes Hahne Bernhard Kuster Julien Gagneur |
spellingShingle |
Basak Eraslan Dongxue Wang Mirjana Gusic Holger Prokisch Björn M Hallström Mathias Uhlén Anna Asplund Frederik Pontén Thomas Wieland Thomas Hopf Hannes Hahne Bernhard Kuster Julien Gagneur Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues Molecular Systems Biology codon usage mRNA sequence motifs proteomics transcriptomics translational control |
author_facet |
Basak Eraslan Dongxue Wang Mirjana Gusic Holger Prokisch Björn M Hallström Mathias Uhlén Anna Asplund Frederik Pontén Thomas Wieland Thomas Hopf Hannes Hahne Bernhard Kuster Julien Gagneur |
author_sort |
Basak Eraslan |
title |
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues |
title_short |
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues |
title_full |
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues |
title_fullStr |
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues |
title_full_unstemmed |
Quantification and discovery of sequence determinants of protein‐per‐mRNA amount in 29 human tissues |
title_sort |
quantification and discovery of sequence determinants of protein‐per‐mrna amount in 29 human tissues |
publisher |
Wiley |
series |
Molecular Systems Biology |
issn |
1744-4292 |
publishDate |
2019-02-01 |
description |
Abstract Despite their importance in determining protein abundance, a comprehensive catalogue of sequence features controlling protein‐to‐mRNA (PTR) ratios and a quantification of their effects are still lacking. Here, we quantified PTR ratios for 11,575 proteins across 29 human tissues using matched transcriptomes and proteomes. We estimated by regression the contribution of known sequence determinants of protein synthesis and degradation in addition to 45 mRNA and 3 protein sequence motifs that we found by association testing. While PTR ratios span more than 2 orders of magnitude, our integrative model predicts PTR ratios at a median precision of 3.2‐fold. A reporter assay provided functional support for two novel UTR motifs, and an immobilized mRNA affinity competition‐binding assay identified motif‐specific bound proteins for one motif. Moreover, our integrative model led to a new metric of codon optimality that captures the effects of codon frequency on protein synthesis and degradation. Altogether, this study shows that a large fraction of PTR ratio variation in human tissues can be predicted from sequence, and it identifies many new candidate post‐transcriptional regulatory elements. |
topic |
codon usage mRNA sequence motifs proteomics transcriptomics translational control |
url |
https://doi.org/10.15252/msb.20188513 |
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