Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada; Alberta RNA Research and Training Institute (ARRTI), Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, Canada.
J Biol Chem. 2024 Aug;300(8):107488. doi: 10.1016/j.jbc.2024.107488. Epub 2024 Jun 20.
Transfer RNAs (tRNAs) are the most highly modified cellular RNAs, both with respect to the proportion of nucleotides that are modified within the tRNA sequence and with respect to the extraordinary diversity in tRNA modification chemistry. However, the functions of many different tRNA modifications are only beginning to emerge. tRNAs have two general clusters of modifications. The first cluster is within the anticodon stem-loop including several modifications essential for protein translation. The second cluster of modifications is within the tRNA elbow, and roles for these modifications are less clear. In general, tRNA elbow modifications are typically not essential for cell growth, but nonetheless several tRNA elbow modifications have been highly conserved throughout all domains of life. In addition to forming modifications, many tRNA modifying enzymes have been demonstrated or hypothesized to also play an important role in folding tRNA acting as tRNA chaperones. In this review, we summarize the known functions of tRNA modifying enzymes throughout the lifecycle of a tRNA molecule, from transcription to degradation. Thereby, we describe how tRNA modification and folding by tRNA modifying enzymes enhance tRNA maturation, tRNA aminoacylation, and tRNA function during protein synthesis, ultimately impacting cellular phenotypes and disease.
转移 RNA（tRNA）是细胞内修饰程度最高的 RNA，无论是从 tRNA 序列中修饰核苷酸的比例，还是从 tRNA 修饰化学的非凡多样性来看，都是如此。然而，许多不同 tRNA 修饰的功能才刚刚开始显现。tRNA 有两个主要的修饰簇。第一个簇位于反密码子茎环内，包括对蛋白质翻译至关重要的几个修饰。第二个修饰簇位于 tRNA 肘内，这些修饰的作用不太清楚。一般来说，tRNA 肘修饰通常不是细胞生长所必需的，但尽管如此，几种 tRNA 肘修饰在所有生命领域都得到了高度保守。除了形成修饰外，许多 tRNA 修饰酶已被证明或假设在折叠 tRNA 方面也发挥着重要作用，充当 tRNA 伴侣。在这篇综述中，我们总结了 tRNA 修饰酶在 tRNA 分子生命周期中的已知功能，从转录到降解。由此，我们描述了 tRNA 修饰和 tRNA 修饰酶的折叠如何增强 tRNA 的成熟、tRNA 的氨酰化以及蛋白质合成过程中 tRNA 的功能，最终影响细胞表型和疾病。
