Rossmanith W, Karwan R M
Institut für Tumorbiologie-Krebsforschung der Universität Wien, PG Genexpression, Austria.
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.
线粒体tRNA基因中的几个点突变已与线粒体疾病的不同临床亚组相关联。在tRNA（Leu）（UUR）基因中发现了特别大量的不同突变。我们发现，位于该tRNA的D环和反密码子茎中的线粒体基因组核苷酸位置3256、3260和3271处的碱基替换，以及改变参与三级相互作用的碱基的3243突变，在体外显著损害了tRNA前体的加工。与其他研究相关，我们的结果表明，线粒体tRNA（Leu）（UUR）某些突变变体的加工效率低下是导致线粒体功能障碍并进而导致疾病的主要分子损伤。
