Hess J F, Parisi M A, Bennett J L, Clayton D A
Department of Developmental Biology, Stanford University School of Medicine, California 94305-5427.
Nature. 1991 May 16;351(6323):236-9. doi: 10.1038/351236a0.
Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
线粒体DNA（mtDNA）缺陷与多种不同的人类疾病相关，包括线粒体脑肌病。这些突变包括缺失，但也有重复和点突变。患有MELAS（线粒体肌病、脑病、乳酸酸中毒和卒中样发作）的个体在转运RNA（Leu（UUR））基因的高度保守部分存在常见的A到G替换。尽管MELAS突变可能与与MERRF（肌阵挛性癫痫伴破碎红纤维）相关的tRNA（Lys）基因突变类似，但它也位于体外16S核糖体RNA 3'末端形成所需的十三聚体序列中间。我们发现，MELAS突变导致16S rRNA转录终止严重受损，这与部分纯化的终止蛋白对MELAS模板的亲和力降低相关。这表明MELAS的分子缺陷是相对于其他线粒体基因产物而言，无法产生正确类型和数量的rRNA。
