Aminoacyl-tRNA synthetases are multivalent suppressors of defects due to human equivalent mutations in yeast mt tRNA genes

Biochim Biophys Acta. 2010 Sep;1803(9):1050-7. doi: 10.1016/j.bbamcr.2010.05.003. Epub 2010 May 13.


The use of the yeast model for the study of the molecular and cellular effects of the pathogenic base substitutions in human mitochondrial tRNA genes has recently been validated by the finding that the suppressing factors identified in yeast (the mitochondrial protein elongation factor EF-Tu and the cognate aminoacyl-tRNA synthetase) have suppressing activities also in human cells. In this paper we report a detailed analysis of the cross-suppressing activities of valyl- and leucyl-tRNA synthetases on different tRNA mutants. Glycerol growth, respiration, Northern analysis consistently show that similar suppressing effects can be obtained by these two yeast synthetases and by the orthologous human enzymes. As a whole the present data indicate that the suppression by mt aa-RS is probably not related to the enzyme activities per se, and may be due to a stabilizing chaperon-like effect of the synthetase molecules on the tRNA structure altered by the mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution / genetics
  • Amino Acyl-tRNA Synthetases / genetics
  • Amino Acyl-tRNA Synthetases / physiology*
  • Base Sequence
  • Cell Respiration / genetics
  • Cell Respiration / physiology
  • Genes, Mitochondrial / genetics*
  • Genes, Tumor Suppressor / physiology
  • Humans
  • Molecular Sequence Data
  • Mutation / physiology
  • Organisms, Genetically Modified
  • Phenotype
  • RNA, Transfer / genetics*
  • Saccharomyces cerevisiae / genetics
  • Yeasts / enzymology
  • Yeasts / genetics*


  • RNA, Transfer
  • Amino Acyl-tRNA Synthetases