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

FEBS Letters

Karwan, Robert M.¹  Rossmanith, Walter¹ 

[1] Institut für Tumorbiologie-Krebsforschung der Universität Wien, PG Genexpression, A-1090 Wien, Austria

关键词: tRNA processing;    RNase P;    Mitochondrial disease;    Mutation;    3′ pre-tRNase;    precursor-tRNA 3′-endonuclease;    MELAS;    mitochondrial myopathy;    encephalopathy;    lactic acidosis;    and stroke-like episodes;    (mt);    mitochondrial;    mtDNA;    mitochondrial DNA;    mtRNase P;    mitochondrial RNase P;    nRNase P;    nuclear RNase P;    PEG;    polyethylene glycol;   

DOI  :  10.1016/S0014-5793(98)00928-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown