Shah Z H, O'Dell K M, Miller S C, An X, Jacobs H T
Institute of Medical Technology, University of Tampere, Finland.
Gene. 1997 Dec 19;204(1-2):55-62. doi: 10.1016/s0378-1119(97)00521-0.
We have characterized nuclear genes for mitoribosomal protein S12 (mt-rps12) a major component of the ribosomal accuracy centre, in human, mouse and Drosophila melanogaster. In human and Drosophila, and probably also in mouse, there is a single intron within the coding region, located in the mitochondrial targeting pre-sequence. In humans, the mRNA structure is highly suggestive of translational regulation. In all three species, there is an amino-acid substitution with respect to eubacterial homologues in a residue implicated in aminoglycoside resistance. The only viable mutant allele of the Drosophila gene, associated with a bang-sensitive phenotype (paralysis upon mechanical vibration, arising from a mechanoreceptor cell defect) also has a novel substitution in a conserved region implicated in translational fidelity. Given the involvement of the mitoribosomal accuracy centre in human sensorineural deafness by virtue of rRNA mutations, our results indicate that this fly mutant may be a useful animal model of this disorder, and earmark the gene for mt-rps12 as a candidate in human hearing impairment.
我们已经对人、小鼠和黑腹果蝇中核糖体精确性中心的主要成分——线粒体核糖体蛋白S12（mt-rps12）的核基因进行了表征。在人类和果蝇中，可能在小鼠中也是如此，编码区域内有一个单一内含子，位于线粒体靶向前序列中。在人类中，mRNA结构强烈提示存在翻译调控。在所有这三个物种中，与氨基糖苷类抗性相关的一个残基相对于真细菌同源物存在氨基酸替换。果蝇基因唯一的存活突变等位基因与一个对巨响敏感的表型（因机械感受器细胞缺陷导致机械振动时麻痹）相关，在一个与翻译保真度相关的保守区域也有一个新的替换。鉴于线粒体核糖体精确性中心因rRNA突变而与人感音神经性耳聋有关，我们的结果表明，这种果蝇突变体可能是这种疾病的有用动物模型，并将mt-rps12基因指定为人类听力障碍的候选基因。
