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- W2616018166 abstract "Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP. Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of the sSNP and rescues protein conformation and function. Our results highlight the wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA translation and provide direct evidence for the central role of cellular tRNA levels in mediating the actions of sSNPs in a tissue-specific manner." @default.
- W2616018166 created "2017-05-26" @default.
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- W2616018166 date "2017-05-16" @default.
- W2616018166 modified "2023-10-18" @default.
- W2616018166 title "Alteration of protein function by a silent polymorphism linked to tRNA abundance" @default.
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- W2616018166 doi "https://doi.org/10.1371/journal.pbio.2000779" @default.
- W2616018166 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5433685" @default.
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- W2616018166 hasPublicationYear "2017" @default.
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