Department of Biology, University of Rochester, Rochester, NY 14627.
Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17350-5. doi: 10.1073/pnas.1313473110. Epub 2013 Sep 30.
The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.
裸鼹鼠(Heterocephalus glaber)是一种地下穴居的真社会性啮齿动物,具有明显的长寿命和抗肿瘤发生能力。多项数据表明蛋白质翻译的调节与寿命有关。在这里,我们报告裸鼹鼠的 28S 核糖体 RNA(rRNA)被加工成两个大小不等的较小片段。两个断点位于 28S rRNA 发散区 6,切除了 263 个核苷酸的片段。该切除片段是裸鼹鼠 rRNA 所特有的,与其他基因组区域没有同源性。由于这个隐藏的断裂位点可能会改变核糖体的结构,我们研究了翻译率和氨基酸掺入保真度是否发生改变。我们报告说,裸鼹鼠成纤维细胞具有显著提高的翻译保真度,尽管其翻译率与小鼠成纤维细胞相当。尽管我们不能直接测试独特的 28S rRNA 结构是否有助于提高翻译的保真度,但我们推测它可能会改变大亚基的折叠或动力学,改变 GTP 水解的速率和/或大亚基与 tRNA 在适应过程中的相互作用,从而影响蛋白质合成的保真度。总之,我们的结果表明,裸鼹鼠细胞产生较少的异常蛋白质,这支持了这样一种假设,即裸鼹鼠更稳定的蛋白质组有助于其长寿。