Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Institute of Applied Physiology, University of Ulm, Albert Einstein Allee 11, 89081 Ulm, Germany; Institute of Anatomy and Cell Biology, Medical Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
J Mol Biol. 2019 Apr 19;431(9):1763-1779. doi: 10.1016/j.jmb.2019.03.004. Epub 2019 Mar 12.
Dysregulation of protein translation is emerging as a unifying mechanism in the pathogenesis of many neuronal disorders. Ribosomal RNA (rRNA) and transfer RNA (tRNA) are structural molecules that have complementary and coordinated functions in protein synthesis. Defects in both rRNAs and tRNAs have been described in mammalian brain development, neurological syndromes, and neurodegeneration. In this review, we present the molecular mechanisms that link aberrant rRNA and tRNA transcription, processing and modifications to translation deficits, and neuropathogenesis. We also discuss the interdependence of rRNA and tRNA biosynthesis and how their metabolism brings together proteotoxic stress and impaired neuronal homeostasis.
蛋白质翻译的失调正在成为许多神经元疾病发病机制的统一机制。核糖体 RNA（rRNA）和转移 RNA（tRNA）是在蛋白质合成中具有互补和协调功能的结构分子。在哺乳动物脑发育、神经综合征和神经退行性变中都已经描述了 rRNA 和 tRNA 的缺陷。在这篇综述中，我们介绍了将异常的 rRNA 和 tRNA 转录、加工和修饰与翻译缺陷和神经发病机制联系起来的分子机制。我们还讨论了 rRNA 和 tRNA 生物合成的相互依赖性，以及它们的代谢如何将蛋白毒性应激和受损的神经元内稳态联系起来。
