tRNAs undergo an extensive maturation process including posttranscriptional modifications that influence secondary and tertiary interactions. Precursor and mature tRNAs lacking key modifications are often recognized as aberrant and subsequently targeted for decay, illustrating the importance of modifications in promoting structural integrity. tRNAs also rely on tRNA chaperones to promote the folding of misfolded substrates into functional conformations. The best characterized tRNA chaperone is the La protein, which interacts with nascent RNA polymerase III transcripts to promote folding and offers protection from exonucleases. More recently, certain tRNA modification enzymes have also been demonstrated to possess tRNA folding activity distinct from their catalytic activity, suggesting that they may act as tRNA chaperones. In this review, we will discuss pioneering studies relating posttranscriptional modification to tRNA stability and decay pathways, present recent advances into the mechanism by which the RNA chaperone La assists pre-tRNA maturation, and summarize emerging research directions aimed at characterizing modification enzymes as tRNA chaperones. Together, these findings shed light on the importance of tRNA folding and how tRNA chaperones, in particular, increase the fraction of nascent pre-tRNAs that adopt a folded, functional conformation.

中文翻译：

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重温 tRNA 伴侣：古老游戏中的新玩家


tRNA 经历广泛的成熟过程，包括影响二级和三级相互作用的转录后修饰。缺乏关键修饰的前体和成熟 tRNA 通常被认为是异常的，随后会被定位为衰变，这说明了修饰在促进结构完整性方面的重要性。 tRNA 还依赖 tRNA 伴侣来促进错误折叠的底物折叠成功能构象。最具特征的 tRNA 伴侣是 La 蛋白，它与新生 RNA 聚合酶 III 转录物相互作用，促进折叠并提供免受核酸外切酶影响的保护。最近，某些 tRNA 修饰酶也被证明具有与其催化活性不同的 tRNA 折叠活性，表明它们可能充当 tRNA 伴侣。在这篇综述中，我们将讨论转录后修饰与 tRNA 稳定性和衰变途径相关的开创性研究，介绍 RNA 伴侣 La 协助前 tRNA 成熟的机制的最新进展，并总结旨在将修饰酶表征为 tRNA 伴侣的新兴研究方向。总之，这些发现揭示了 tRNA 折叠的重要性，以及 tRNA 伴侣如何增加采用折叠功能构象的新生前 tRNA 的比例。