Impairment of tRNA processing by point mutations in mitochondrial tRNA(Leu)(UUR) associated with mitochondrial diseases

FEBS Lett. 1998 Aug 21;433(3):269-74. doi: 10.1016/s0014-5793(98)00928-4.


Several point mutations in mitochondrial tRNA genes have been linked to distinct clinical subgroups of mitochondrial diseases. A particularly large number of different mutations is found in the tRNA(Leu)(UUR) gene. We show that base substitutions at nucleotide position 3256, 3260, and 3271 of the mitochondrial genome, located in the D and anticodon stem of this tRNA, and mutation 3243 changing a base involved in a tertiary interaction, significantly impair the processing of the tRNA precursor in vitro. In correlation with other studies, our results suggest that inefficient processing of certain mutant variants of mitochondrial tRNA(Leu)(UUR) is a primary molecular impairment leading to mitochondrial dysfunction and consequently to disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticodon
  • Base Sequence
  • Codon
  • Endoribonucleases / metabolism*
  • Genetic Diseases, Inborn / genetics*
  • Genetic Variation
  • Humans
  • Mitochondrial Myopathies / genetics*
  • Molecular Sequence Data
  • Nucleic Acid Conformation*
  • Point Mutation*
  • RNA / genetics*
  • RNA / metabolism
  • RNA, Catalytic / metabolism*
  • RNA, Mitochondrial
  • RNA, Transfer, Leu / chemistry
  • RNA, Transfer, Leu / genetics*
  • RNA, Transfer, Leu / metabolism*
  • Ribonuclease P


  • Anticodon
  • Codon
  • RNA, Catalytic
  • RNA, Mitochondrial
  • RNA, Transfer, Leu
  • RNA
  • Endoribonucleases
  • RPP14 protein, human
  • Ribonuclease P