Sekulovski Samoil, Trowitzsch Simon
Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Strasse 9, D-60438 Frankfurt/Main, Germany.
Biol Chem. 2022 Jun 21;403(8-9):749-763. doi: 10.1515/hsz-2021-0406. Print 2022 Jul 26.
Transfer RNAs (tRNAs) are highly structured non-coding RNAs which play key roles in translation and cellular homeostasis. tRNAs are initially transcribed as precursor molecules and mature by tightly controlled, multistep processes that involve the removal of flanking and intervening sequences, over 100 base modifications, addition of non-templated nucleotides and aminoacylation. These molecular events are intertwined with the nucleocytoplasmic shuttling of tRNAs to make them available at translating ribosomes. Defects in tRNA processing are linked to the development of neurodegenerative disorders. Here, we summarize structural aspects of tRNA processing steps with a special emphasis on intron-containing tRNA splicing involving tRNA splicing endonuclease and ligase. Their role in neurological pathologies will be discussed. Identification of novel RNA substrates of the tRNA splicing machinery has uncovered functions unrelated to tRNA processing. Future structural and biochemical studies will unravel their mechanistic underpinnings and deepen our understanding of neurological diseases.
转运RNA（tRNA）是高度结构化的非编码RNA，在翻译和细胞内稳态中发挥关键作用。tRNA最初作为前体分子转录而成，并通过严格控制的多步骤过程成熟，这些过程包括去除侧翼和间隔序列、超过100种碱基修饰、添加非模板化核苷酸以及氨酰化。这些分子事件与tRNA的核质穿梭相互交织，使其能够在翻译核糖体处发挥作用。tRNA加工缺陷与神经退行性疾病的发生有关。在这里，我们总结了tRNA加工步骤的结构方面，特别强调了涉及tRNA剪接内切酶和连接酶的含内含子tRNA剪接。将讨论它们在神经病理学中的作用。tRNA剪接机制新RNA底物的鉴定揭示了与tRNA加工无关的功能。未来的结构和生化研究将揭示其机制基础，并加深我们对神经疾病的理解。
