Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Division of Biochemistry, Mannheim Institute for Innate Immunoscience (MI3), Mannheim Cancer Center (MCC), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Bioessays. 2024 Sep;46(9):e2400107. doi: 10.1002/bies.202400107. Epub 2024 Jul 11.
Post-transcriptional tRNA modifications contribute to the decoding efficiency of tRNAs by supporting codon recognition and tRNA stability. Recent work shows that the molecular and cellular functions of tRNA modifications and tRNA-modifying-enzymes are linked to brain development and neurological disorders. Lack of these modifications affects codon recognition and decoding rate, promoting protein aggregation and translational stress response pathways with toxic consequences to the cell. In this review, we discuss the peculiarity of local translation in neurons, suggesting a role for fine-tuning of translation performed by tRNA modifications. We provide several examples of tRNA modifications involved in physiology and pathology of the nervous system, highlighting their effects on protein translation and discussing underlying mechanisms, like the unfolded protein response (UPR), ribosome quality control (RQC), and no-go mRNA decay (NGD), which could affect neuronal functions. We aim to deepen the understanding of the roles of tRNA modifications and the coordination of these modifications with the protein translation machinery in the nervous system.
转录后 tRNA 修饰通过支持密码子识别和 tRNA 稳定性，有助于提高 tRNA 的解码效率。最近的研究表明，tRNA 修饰和 tRNA 修饰酶的分子和细胞功能与大脑发育和神经紊乱有关。缺乏这些修饰会影响密码子识别和解码速度，促进蛋白质聚集和翻译应激反应途径，对细胞产生毒性后果。在这篇综述中，我们讨论了神经元中局部翻译的特殊性，提出了通过 tRNA 修饰来精细调控翻译的作用。我们提供了几个涉及神经系统生理和病理的 tRNA 修饰的例子，强调了它们对蛋白质翻译的影响，并讨论了潜在的机制，如未折叠蛋白反应 (UPR)、核糖体质量控制 (RQC) 和无意义 mRNA 降解 (NGD)，这些机制可能会影响神经元功能。我们的目的是加深对 tRNA 修饰的作用以及这些修饰与神经系统中蛋白质翻译机制的协调的理解。
