Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients
Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients
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DOI：
10.1093/hmg/9.4.467
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发表时间：
2000-03-01
影响因子：
3.5
通讯作者：
Pääbo, S
中科院分区：
文献类型：
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作者：
Börner, GV;Zeviani, M;Pääbo, S
人类线粒体tRNA基因的突变与许多多系统疾病有关。我们使用tRNA氧化和循环相结合的方法，分别测定了MELAS综合征(线粒体肌病、脑病、乳酸中毒、卒中样发作)和MERRF综合征(肌阵挛癫痫伴粗糙的红色纤维)患者组织样本中突变型和野生型tRNA氨基酰化的相对数量和状态。在大多数但不是所有携带线粒体tRNA(Leu(UUR))基因A3243G替换的MELAS患者的活检组织中，突变的tRNA在加工和/或氨基酰化的tRNA中表达不足，相反，在携带tRNA(Lys)基因A8344G替换的MERRF患者的活检组织中，突变的tRNA的相对丰度和氨基酰化都没有受到影响。因此，虽然A3243G突变可能通过减少氨基酰化tRNA(Leu)的数量而参与MELAS的发病，但A8344G突变不会以同样的方式影响tRNA(Lys)的功能。
Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and MERRF syndrome (myoclonus epilepsy with ragged red fibers), respectively. In most, but not all, biopsies from MELAS patients carrying the A3243G substitution in the mitochondrial tRNA(Leu(UUR)) gene, the mutant tRNA is under-represented among processed and/or aminoacylated tRNAs, In contrast, in biopsies from MERRF patients harboring the A8344G substitution in the tRNA(Lys) gene neither the relative abundance nor the aminoacylation of the mutated tRNA is affected. Thus, whereas the A3243G mutation may contribute to the pathogenesis of MELAS by reducing the amount of aminoacylated tRNA(Leu), the A8344G mutation does not affect tRNA(Lys) function in the same way.