Assessing cell-specific effects of genetic variations using tRNA microarrays
Abstract Background By definition, effect of synonymous single-nucleotide variants (SNVs) on protein folding and function are neutral, as they alter the codon and not the encoded amino acid. Recent examples indicate tissue-specific and transfer RNA (tRNA)-dependent effects of some genetic variations...
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doaj-3cbbce1c6eb74632b9d6448a1ea289bd2020-11-25T03:47:11ZengBMCBMC Genomics1471-21642019-07-0120S811210.1186/s12864-019-5864-1Assessing cell-specific effects of genetic variations using tRNA microarraysChristine Polte0Daniel Wedemeyer1Kathryn E. Oliver2Johannes Wagner3Marcel J. C. Bijvelds4John Mahoney5Hugo R. de Jonge6Eric J. Sorscher7Zoya Ignatova8Biochemistry and Molecular Biology, Department of Chemistry, University of HamburgBiochemistry and Molecular Biology, Department of Chemistry, University of HamburgEmory University School of MedicineBiochemistry and Molecular Biology, Department of Chemistry, University of HamburgGastroenterology and Hepatology Erasmus MC University Medical CenterCystic Fibrosis Foundation CFFT LabGastroenterology and Hepatology Erasmus MC University Medical CenterEmory University School of MedicineBiochemistry and Molecular Biology, Department of Chemistry, University of HamburgAbstract Background By definition, effect of synonymous single-nucleotide variants (SNVs) on protein folding and function are neutral, as they alter the codon and not the encoded amino acid. Recent examples indicate tissue-specific and transfer RNA (tRNA)-dependent effects of some genetic variations arguing against neutrality of synonymous SNVs for protein biogenesis. Results We performed systematic analysis of tRNA abunandance across in various models used in cystic fibrosis (CF) research and drug development, including Fischer rat thyroid (FRT) cells, patient-derived primary human bronchial epithelia (HBE) from lung biopsies, primary human nasal epithelia (HNE) from nasal curettage, intestinal organoids, and airway progenitor-directed differentiation of human induced pluripotent stem cells (iPSCs). These were compared to an immortalized CF bronchial cell model (CFBE41o−) and two widely used laboratory cell lines, HeLa and HEK293. We discovered that specific synonymous SNVs exhibited differential effects which correlated with variable concentrations of cognate tRNAs. Conclusions Our results highlight ways in which the presence of synonymous SNVs may alter local kinetics of mRNA translation; and thus, impact protein biogenesis and function. This effect is likely to influence results from mechansistic analysis and/or drug screeining efforts, and establishes importance of cereful model system selection based on genetic variation profile.http://link.springer.com/article/10.1186/s12864-019-5864-1Nucleotide variantsSynonymous single nucleotide polymorphismstRNAProtein translationCystic fibrosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Christine Polte Daniel Wedemeyer Kathryn E. Oliver Johannes Wagner Marcel J. C. Bijvelds John Mahoney Hugo R. de Jonge Eric J. Sorscher Zoya Ignatova |
spellingShingle |
Christine Polte Daniel Wedemeyer Kathryn E. Oliver Johannes Wagner Marcel J. C. Bijvelds John Mahoney Hugo R. de Jonge Eric J. Sorscher Zoya Ignatova Assessing cell-specific effects of genetic variations using tRNA microarrays BMC Genomics Nucleotide variants Synonymous single nucleotide polymorphisms tRNA Protein translation Cystic fibrosis |
author_facet |
Christine Polte Daniel Wedemeyer Kathryn E. Oliver Johannes Wagner Marcel J. C. Bijvelds John Mahoney Hugo R. de Jonge Eric J. Sorscher Zoya Ignatova |
author_sort |
Christine Polte |
title |
Assessing cell-specific effects of genetic variations using tRNA microarrays |
title_short |
Assessing cell-specific effects of genetic variations using tRNA microarrays |
title_full |
Assessing cell-specific effects of genetic variations using tRNA microarrays |
title_fullStr |
Assessing cell-specific effects of genetic variations using tRNA microarrays |
title_full_unstemmed |
Assessing cell-specific effects of genetic variations using tRNA microarrays |
title_sort |
assessing cell-specific effects of genetic variations using trna microarrays |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2019-07-01 |
description |
Abstract Background By definition, effect of synonymous single-nucleotide variants (SNVs) on protein folding and function are neutral, as they alter the codon and not the encoded amino acid. Recent examples indicate tissue-specific and transfer RNA (tRNA)-dependent effects of some genetic variations arguing against neutrality of synonymous SNVs for protein biogenesis. Results We performed systematic analysis of tRNA abunandance across in various models used in cystic fibrosis (CF) research and drug development, including Fischer rat thyroid (FRT) cells, patient-derived primary human bronchial epithelia (HBE) from lung biopsies, primary human nasal epithelia (HNE) from nasal curettage, intestinal organoids, and airway progenitor-directed differentiation of human induced pluripotent stem cells (iPSCs). These were compared to an immortalized CF bronchial cell model (CFBE41o−) and two widely used laboratory cell lines, HeLa and HEK293. We discovered that specific synonymous SNVs exhibited differential effects which correlated with variable concentrations of cognate tRNAs. Conclusions Our results highlight ways in which the presence of synonymous SNVs may alter local kinetics of mRNA translation; and thus, impact protein biogenesis and function. This effect is likely to influence results from mechansistic analysis and/or drug screeining efforts, and establishes importance of cereful model system selection based on genetic variation profile. |
topic |
Nucleotide variants Synonymous single nucleotide polymorphisms tRNA Protein translation Cystic fibrosis |
url |
http://link.springer.com/article/10.1186/s12864-019-5864-1 |
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