tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease

IF 5.3 2区医学 Q2 CELL BIOLOGY Cell Biology and Toxicology Pub Date : 2024-09-14 DOI:10.1007/s10565-024-09919-9

Di Wu, Xiuling Li, Faheem Ahmed Khan, Chenyang Yuan, Nuruliarizki Shinta Pandupuspitasari, Chunjie Huang, Fei Sun, Kaifeng Guan

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Abstract

tRNAs are codon decoders that convert the transcriptome into the proteome. The field of tRNA research is excited by the increasing discovery of specific tRNA modifications that are installed at specific, evolutionarily conserved positions by a set of specialized tRNA-modifying enzymes and the biogenesis of tRNA-derived regulatory fragments (tsRNAs) which exhibit copious activities through multiple mechanisms. Dysregulation of tRNA modification usually has pathological consequences, a phenomenon referred to as "tRNA modopathy". Current evidence suggests that certain tRNA-modifying enzymes and tsRNAs may serve as promising diagnostic biomarkers and therapeutic targets, particularly for chemoresistant cancers. In this review, we discuss the latest discoveries that elucidate the molecular mechanisms underlying the functions of clinically relevant tRNA modifications and tsRNAs, with a focus on malignancies. We also discuss the therapeutic potential of tRNA/tsRNA-based therapies, aiming to provide insights for the development of innovative therapeutic strategies. Further efforts to unravel the complexities inherent in tRNA biology hold the promise of yielding better biomarkers for the diagnosis and prognosis of diseases, thereby advancing the development of precision medicine for health improvement.

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tRNA 修饰和 tRNA 衍生的小 RNA：对人类疾病中 tRNA 的新认识

tRNA 是将转录组转化为蛋白质组的密码子解码器。越来越多的人发现了特异性 tRNA 修饰，这些修饰由一组特异性 tRNA 修饰酶安装在特定的、进化上保守的位置上，同时还发现了 tRNA 衍生的调控片段（tsRNAs）的生物生成，这些片段通过多种机制表现出丰富的活性，从而推动了 tRNA 研究领域的发展。tRNA 修饰失调通常会导致病理后果，这种现象被称为 "tRNA 修饰病"。目前的证据表明，某些 tRNA 修饰酶和 tsRNA 可作为有前途的诊断生物标志物和治疗靶点，尤其是对化疗耐药的癌症。在这篇综述中，我们讨论了阐明临床相关 tRNA 修饰和 tsRNA 功能的分子机制的最新发现，重点是恶性肿瘤。我们还讨论了基于 tRNA/tsRNA 的疗法的治疗潜力，旨在为创新治疗策略的开发提供见解。进一步努力揭示 tRNA 生物学固有的复杂性，有望为疾病的诊断和预后提供更好的生物标志物，从而推动精准医学的发展，改善健康状况。

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.