@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{ZhangFedyuninMiekleyetal.2010,
  author    = {Zhang, Gong and Fedyunin, Ivan and Miekley, Oskar and Valleriani, Angelo and Moura, Alessandro and Ignatova, Zoya},
  title     = {Global and local depletion of ternary complex limits translational elongation},
  issn      = {0305-1048},
  doi       = {10.1093/Nar/Gkq196},
  year      = {2010},
  abstract  = {The translation of genetic information according to the sequence of the mRNA template occurs with high accuracy and fidelity. Critical events in each single step of translation are selection of transfer RNA (tRNA), codon reading and tRNA-regeneration for a new cycle. We developed a model that accurately describes the dynamics of single elongation steps, thus providing a systematic insight into the sensitivity of the mRNA translation rate to dynamic environmental conditions. Alterations in the concentration of the aminoacylated tRNA can transiently stall the ribosomes during translation which results, as suggested by the model, in two outcomes: either stress-induced change in the tRNA availability triggers the premature termination of the translation and ribosomal dissociation, or extensive demand for one tRNA species results in a competition between frameshift to an aberrant open-reading frame and ribosomal drop-off. Using the bacterial Escherichia coli system, we experimentally draw parallels between these two possible mechanisms.},
  language  = {en}
}