Dataset Information

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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Publications

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.

Background

Results

Conclusions

Publications

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

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