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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 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.

SUBMITTER: Polte C

PROVIDER: S-EPMC6632033 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Assessing cell-specific effects of genetic variations using tRNA microarrays.

Polte Christine C Wedemeyer Daniel D Oliver Kathryn E KE Wagner Johannes J Bijvelds Marcel J C MJC Mahoney John J de Jonge Hugo R HR Sorscher Eric J EJ Ignatova Zoya Z

BMC genomics 20190716 Suppl 8

<h4>Background</h4>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.<h4>Results</h4>We performed systematic analysis of tRNA abunandance across in various models used in cystic fibrosis (CF) research ...[more]

PMID: 31307398

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Dataset Information

Assessing cell-specific effects of genetic variations using tRNA microarrays.

Publications

Assessing cell-specific effects of genetic variations using tRNA microarrays.

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