某些与线粒体脑肌病伴乳酸血症和卒中样发作（MELAS）相关的突变导致线粒体亮氨酰-tRNA（UUR）氨酰化作用降低。

Reduction of mitochondrial tRNALeu(UUR) aminoacylation by some MELAS-associated mutations.

作者信息

Hao Rui, Yao Yong-Neng, Zheng Yong-Gang, Xu Min-Gang, Wang En-Duo

机构信息

State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, PR China.

出版信息

FEBS Lett. 2004 Dec 3;578(1-2):135-9. doi: 10.1016/j.febslet.2004.11.004.

DOI:10.1016/j.febslet.2004.11.004

PMID:15581630

Abstract

The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome (MELAS) is a rare congenital disorder of mitochondrial DNA. Five single nucleotide substitutions within the human mitochondrial tRNALeu(UUR) gene have been reported to be associated with MELAS. Here, we provide in vitro evidence that the aminoacylation capacities of these five hmtRNALeu(UUR) transcripts are reduced to different extents relative to the wild-type hmtRNALeu(UUR) transcript. A thermal denaturation experiment showed that the A3243G and T3291C mutants, which were the least charged by LeuRS, have fragile structures. In addition, the T3291C mutant can inhibit aminoacylation of the wild-type hmtRNALeu(UUR), indicating that it may act as an inhibitor in the mitochondrial heteroplasmic environment.

摘要

线粒体肌病、脑病、乳酸酸中毒和卒中样发作综合征（MELAS）是一种罕见的线粒体DNA先天性疾病。据报道，人类线粒体tRNALeu(UUR)基因内的五个单核苷酸替换与MELAS相关。在此，我们提供体外证据表明，相对于野生型hmtRNALeu(UUR)转录本，这五种hmtRNALeu(UUR)转录本的氨酰化能力在不同程度上降低。热变性实验表明，由亮氨酰-tRNA合成酶（LeuRS）负载最少的A3243G和T3291C突变体结构不稳定。此外，T3291C突变体可抑制野生型hmtRNALeu(UUR)的氨酰化，表明它可能在线粒体异质性环境中充当抑制剂。