与人类疾病相关的几种线粒体氨基酰-tRNA合成酶

Mitochondrial Aminoacyl-tRNA Synthetases Related to Human Diseases

氨基酰-tRNA合成酶是一类古老的蛋白质,催化蛋白质生物合成中的第一步反应.已经发现氨基酰-tRNA合成酶还参与大量的其他生命过程,如编校、tRNA的成熟与转运、RNA的剪切、细胞因子等功能.最近的研究结果表明,线粒体氨基酰-tRNA合成酶与人类的疾病密切相关.人线粒体精氨酰-tRNA合成酶基因2号内含子中的一个单点突变导致该基因的转录本被异常剪接,造成脑桥小脑发育不全.人线粒体天冬氨酰-tRNA合成酶基因上的一系列突变致使其mRNA被快速降解或者蛋白质氨基酸一级结构的改变,导致脑干脊髓白质病变及乳糖增高症.人线粒体亮氨酰-tRNA合成酶基因的一个单核苷酸多态性与2型糖尿病密切相关.这些研究结果进一步增强了我们对于氨基酰-tRNA合成酶的生物学功能的认识,并将促进对由线粒体氨基酰-tRNA合成酶所引起线粒体病的致病机理以及治疗方法的研究.

Aminoacyl-tRNA synthetase is a class of ancient proteins, catalyzing the first reaction of protein biosynthesis. It has been found that they also participate in a lot of other cellular processes such as editing, tRNA maturation and transfer, RNA cleavage and function as cellular factors. Recent studies showed that some mitochondrial aminoacyl-tRNA synthetases are closely related with human diseases. A single point mutation in intervening sequence 2 （IVS2） of human mitochondrial arginyl-tRNA synthetase gene causes abnormal cleavage of its transcript, resulting in pontocerebellar hypoplasia. A series of mutations in human mitochondrial aspartyl-tRNA synthetase gene cause rapid decay of its mRNA or alteration in protein primary sequence, leading to leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. A single nucleotide polymorphism in human mitochondrial leucyl-tRNA synthetase is significantly associated with type 2 diabetes. These results further enhance our understanding about the cellular function of aminoacyl-tRNA synthetase and promote studies toward the mechanism and therapy of aminoacyl-tRNA synthetase-causing mitochondrial diseases.