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Alteration of protein function by a silent polymorphism linked to tRNA abundance
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نویسنده
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kirchner s. ,cai z. ,rauscher r. ,kastelic n. ,anding m. ,czech a. ,kleizen b. ,ostedgaard l.s. ,braakman i. ,sheppard d.n. ,ignatova z.
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منبع
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plos biology - 2017 - دوره : 15 - شماره : 5
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چکیده
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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. © 2017 public library of science. all rights reserved.
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آدرس
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biochemistry,institute of biochemistry and biology,university of potsdam,potsdam,germany,wellcome centre for molecular parasitology,institute of infection,immunity and inflammation,university of glasgow,glasgow, United Kingdom, school of physiology,pharmacology and neuroscience,university of bristol,bristol, United Kingdom, institute for biochemistry and molecular biology,department of chemistry,university of hamburg,hamburg, Germany, biochemistry,institute of biochemistry and biology,university of potsdam,potsdam, Germany, biochemistry,institute of biochemistry and biology,university of potsdam,potsdam, Germany, institute for biochemistry and molecular biology,department of chemistry,university of hamburg,hamburg, Germany, cellular protein chemistry,department of chemistry,bijvoet center for biomolecular research,utrecht university,utrecht, Netherlands, department of internal medicine,university of iowa,iowa city,ia, United States, cellular protein chemistry,department of chemistry,bijvoet center for biomolecular research,utrecht university,utrecht, Netherlands, school of physiology,pharmacology and neuroscience,university of bristol,bristol, United Kingdom, biochemistry,institute of biochemistry and biology,university of potsdam,potsdam,germany,institute for biochemistry and molecular biology,department of chemistry,university of hamburg,hamburg, Germany
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Authors
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