Molecular phenotype of a human lymphoblastoid cell-line homoplasmic for the np 7445 deafness-associated mitochondrial mutation

被引:41
作者
Reid, FM
Rovio, A
Holt, IJ
Jacobs, HT
机构
[1] TAMPERE UNIV, INST MED TECHNOL, FIN-33101 TAMPERE, FINLAND
[2] UNIV GLASGOW, INST BIOMED & LIFE SCI, DIV MOL GENET, GLASGOW G11 6NU, LANARK, SCOTLAND
[3] UNIV DUNDEE, NINEWELLS HOSP, DEPT BIOCHEM MED, DUNDEE DD1 9SY, SCOTLAND
关键词
D O I
10.1093/hmg/6.3.443
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have studied mitochondrial gene expression and metabolic function in a human lymphoblastoid cell-line homoplasmic for the np 7445, deafness-associated mitochondrial DNA mutation, The mutation maps to the 3' termini of the oppositely oriented genes encoding cytochrome oxidase subunit I (COI) and tRNA-ser(UCN), In comparison with control lymphoblastoid cells, we detected a marked depletion (>60%) of tRNA-ser(UCN), There was, however, no significant impairment of respiratory function, no alteration to the structure or abundance of COI mRNA or its precursors, and no detectable abnormality of mitochondrial protein synthesis, We also found considerable tissue-variation in the abundance of tRNA-ser(UCN), We propose that the tissue-specific phenotype associated with this mutation results from an inherent deficiency in the processing of the mutant pre-tRNA, that becomes limiting for protein synthesis only in a restricted set of cells of the auditory system in which the tRNA is, for other reasons, already at a critically low level.
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页码:443 / 449
页数:7
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