Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations
文献类型：期刊论文
| 作者 | Wang, M; Zhou, XL; Liu, RJ; Fang, ZP; Zhou, M; Eriani, G; Wang, ED |
| 刊名 | BIOCHEMICAL JOURNAL
 |
| 出版日期 | 2013 |
| 卷号 | 453期号:1页码:455-465 |
| 关键词 | CCA-adding modification elongation factor Tu (EF-Tu) mitochondria pathogenicity tRNA |
| 通讯作者 | Eriani, G (reprint author), Univ Strasbourg, CNRS, Inst Biol Mol & Cellulaire, Architecture & React ARN, 15 Rue Rene Descartes, F-67084 Strasbourg, France.,g.eriani@ibmc-cnrs.unistra.fr ; edwang@sibcb.ac.cn |
| 英文摘要 | Point mutations in hmtRNAs (human mitochondrial tRNAs) can cause various disorders, such as CPEO (chronic progressive external ophthalmoplegia) and MM (mitochondrial myopathy). Mitochondrial tRNA(Leu), especially the UUR codon isoacceptor, is recognized as a hot spot for pathogenic mtDNA point mutations. Thus far, 40 mutations have been reported in hmtRNAs(Leu). In the present paper, we describe the wide range of effects of two substitutions found in the T Psi C arms of two hmtRNAs(Leu) isoacceptors. The G52A substitution, corresponding to the pathogenic G12315A mutation in tRNA(Leu) (CUN), and G3283A in tRNA(Leu) (UUR) exhibited structural changes in the outer corner of the tRNA shape as shown by RNase probing. These mutations also induced reductions in aminoacylation, 3'-end processing and base modification processes. The main effects of the A57G substitution, corresponding to mutations Al2320G in tRNA(Leu)(CUN) and A3288G in tRNA(Leu)(UUR), were observed on the aminoacylation activity and binding to hmEF-Tu (human mitochondrial elongation factor Tu). These observations suggest that the wide range of effects may amplify the deleterious impact on mitochondrial protein synthesis in vivo. The findings also emphasize that an exact understanding of tRNA dysfunction is critical for the future development of therapies for mitochondrial diseases. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | ELONGATION-FACTOR TU ; ESCHERICHIA-COLI ; MODIFIED NUCLEOTIDES ; CRYSTAL-STRUCTURE ; SPORADIC PATIENT ; TERNARY COMPLEX ; SKELETAL-MUSCLE ; MTDNA MUTATION ; AMINO-ACIDS ; AMINOACYLATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000322358700014 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/511]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Wang, M,Zhou, XL,Liu, RJ,et al. Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations[J]. BIOCHEMICAL JOURNAL,2013,453(1):455-465. |
| APA | Wang, M.,Zhou, XL.,Liu, RJ.,Fang, ZP.,Zhou, M.,...&Wang, ED.(2013).Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations.BIOCHEMICAL JOURNAL,453(1),455-465. |
| MLA | Wang, M,et al."Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations".BIOCHEMICAL JOURNAL 453.1(2013):455-465. |
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