@phdthesis{Czech2013,
  author    = {Czech, Andreas},
  title     = {Variations in the tRNA pool of mammalian cells upon differentiation and oxidative stress},
  address   = {Potsdam},
  pages     = {98 S.},
  year      = {2013},
  language  = {en}
}
@article{CzechFedyuninZhangetal.2010,
  author    = {Czech, Andreas and Fedyunin, Ivan and Zhang, Gong and Ignatova, Zoya},
  title     = {Silent mutations in sight : co-variations in tRNA abundance as a key to unravel consequences of silent mutations},
  issn      = {1742-206X},
  doi       = {10.1039/C004796c},
  year      = {2010},
  abstract  = {Mutations that alter the amino acid sequence are known to potentially exert deleterious effects on protein function, whereas substitutions of nucleotides without amino acid change are assumed to be neutral for the protein's functionality. However, cumulative evidence suggests that synonymous substitutions might also induce phenotypic variability by affecting splicing accuracy, translation fidelity, and conformation and function of proteins. tRNA isoacceptors mediate the translation of codons to amino acids, and asymmetric tRNA abundance causes variations in the rate of translation of each single triplet. Consequently, the effect of a silent point mutation in the coding region could be significant due to differential abundances of the cognate tRNA(s), emphasizing the importance of precise assessment of tRNA composition. Here, we provide an overview of the methods used to quantitatively determine the concentrations of tRNA species and discuss synonymous mutations in the context of tRNA composition of the cell, thus providing a new twist on the detrimental impact of the silent mutations.},
  language  = {en}
}
@article{CzechWendeMoerletal.2013,
  author    = {Czech, Andreas and Wende, Sandra and Moerl, Mario and Pan, Tao and Ignatova, Zoya},
  title     = {Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress},
  series = {PLoS Genetics : a peer-reviewed, open-access journal},
  volume    = {9},
  journal   = {PLoS Genetics : a peer-reviewed, open-access journal},
  number    = {8},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003767},
  pages     = {9},
  year      = {2013},
  abstract  = {Stress-induced changes of gene expression are crucial for survival of eukaryotic cells. Regulation at the level of translation provides the necessary plasticity for immediate changes of cellular activities and protein levels. In this study, we demonstrate that exposure to oxidative stress results in a quick repression of translation by deactivation of the aminoacylends of all transfer-RNA (tRNA). An oxidative-stress activated nuclease, angiogenin, cleaves first within the conserved single-stranded 3'-CCA termini of all tRNAs, thereby blocking their use in translation. This CCA deactivation is reversible and quickly repairable by the CCA-adding enzyme [ATP(CTP): tRNA nucleotidyltransferase]. Through this mechanism the eukaryotic cell dynamically represses and reactivates translation at low metabolic costs.},
  language  = {en}
}
@article{GirstmairSaffertRodeetal.2013,
  author    = {Girstmair, Hannah and Saffert, Paul and Rode, Sascha and Czech, Andreas and Holland, Gudrun and Bannert, Norbert and Ignatova, Zoya},
  title     = {Depletion of Cognate Charged Transfer RNA Causes Translational Frameshifting within the Expanded CAG Stretch in Huntingtin},
  series = {Cell reports},
  volume    = {3},
  journal   = {Cell reports},
  number    = {1},
  publisher = {Cell Press},
  address   = {Cambridge},
  issn      = {2211-1247},
  doi       = {10.1016/j.celrep.2012.12.019},
  pages     = {148 -- 159},
  year      = {2013},
  abstract  = {Huntington disease (HD), a dominantly inherited neurodegenerative disorder caused by the expansion of a CAG-encoded polyglutamine (polyQ) repeat in huntingtin (Htt), displays a highly heterogeneous etiopathology and disease onset. Here, we show that the translation of expanded CAG repeats in mutant Htt exon 1 leads to a depletion of charged glutaminyl-transfer RNA (tRNA) Gln-CUG that pairs exclusively to the CAG codon. This results in translational frameshifting and the generation of various transframe-encoded species that differently modulate the conformational switch to nucleate fibrillization of the parental polyQ protein. Intriguingly, the frameshifting frequency varies strongly among different cell lines and is higher in cells with intrinsically lower concentrations of tRNA Gln-CUG. The concentration of tRNA Gln-CUG also differs among different brain areas in the mouse. We propose that translational frameshifting may act as a significant disease modifier that contributes to the cell-selective neurotoxicity and disease course heterogeneity of HD on both cellular and individual levels.},
  language  = {en}
}
@article{KirchnerCaiRauscheretal.2017,
  author    = {Kirchner, Sebastian and Cai, Zhiwei and Rauscher, Robert and Kastelic, Nicolai and Anding, Melanie and Czech, Andreas and Kleizen, Bertrand and Ostedgaard, Lynda S. and Braakman, Ineke and Sheppard, David N. and Ignatova, Zoya},
  title     = {Alteration of protein function by a silent polymorphism linked to tRNA abundance},
  series = {PLoS biology},
  volume    = {15},
  journal   = {PLoS biology},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1545-7885},
  doi       = {10.1371/journal.pbio.2000779},
  pages     = {29},
  year      = {2017},
  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.},
  language  = {en}
}