Impairment of tRNA processing by point mutations in mitochondrial tRNALeu(UUR) associated with mitochondrial diseases
- 21 August 1998
- journal article
- Published by Wiley in FEBS Letters
- Vol. 433 (3), 269-274
- https://doi.org/10.1016/s0014-5793(98)00928-4
Abstract
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 tRNALeu(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 tRNALeu(UUR) is a primary molecular impairment leading to mitochondrial dysfunction and consequently to disease.Keywords
This publication has 54 references indexed in Scilit:
- Characterization of Human Mitochondrial RNase P: Novel Aspects in tRNA ProcessingBiochemical and Biophysical Research Communications, 1998
- Mitochondrial Encephalomyopathy Associated with a Novel Mutation in the Mitochondrial tRNAleu(UUR)Gene (A3243T)Biochemical and Biophysical Research Communications, 1997
- Processing of human mitochondrial tRNAGCUSer(AGY): a novel pathway in tRNA biosynthesisJournal of Molecular Biology, 1997
- tRNA processing in human mitochondrial disordersMolecular Biology Reports, 1996
- Analysis of cybrids harboring MELAS mutations in the mitochondrial tRNALeu(UUR) geneMuscle & Nerve, 1995
- A New Point Mutation at Nucleotide Pair-3291 of the Mitochondrial Transfer-RNALeu(Uur) Gene in a Patient with Mitochondrial Myopathy, Encephalopathy, Lactic-Acidosis, and Stroke-Like Episodes (MELAS)Biochemical and Biophysical Research Communications, 1994
- Accumulation of mtDNA with a Mutation at Position 3271 in tRNALeu(UUR) Gene Introduced from a Melas Patient to HeLa Cells Lacking mtDNA Results in Progressive Inhibition of Mitochondrial Respiratory FunctionBiochemical and Biophysical Research Communications, 1993
- A new mtDNA mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1991
- Distinct clustering of point mutations in mitochondrial DNA among patients with mitochondrial encephalomyopathies and with Parkinson's diseaseBiochemical and Biophysical Research Communications, 1991
- A point mutation in the mitochondrial tRNALeu(UUR) gene in melas (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)Biochemical and Biophysical Research Communications, 1990