Deciphering the pseudouridine nucleobase modification in human diseases: From molecular mechanisms to clinical perspectives

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-01-20 DOI:10.1002/ctm2.70190

Shiheng Jia, Xue Yu, Na Deng, Chen Zheng, Mingguang Ju, Fanglin Wang, Yixiao Zhang, Ziming Gao, Yanshu Li, Heng Zhou, Kai Li

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引用次数: 0

Abstract

RNA pseudouridylation, a dynamic and reversible post-transcriptional modification found in diverse RNA species, is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre-mRNA splicing, enhancement of mRNA translation, and translational fidelity. Disruption of pseudouridylation impairs cellular homeostasis, contributing to pathological alterations. Recent studies have highlighted its regulatory role in human diseases, particularly in tumourigenesis. Cellular stresses trigger RNA pseudouridylation in organisms, suggesting that pseudouridylation-mediated epigenetic reprogramming is essential for maintaining cellular viability and responding to stress. This review examines the regulatory mechanisms and pathological implications of pseudouridylation in human diseases, with a focus on its involvement in tumourigenesis. Additionally, it explores the therapeutic potential of targeting pseudouridylation, presenting novel strategies for disease treatment.

Highlights

Methods to detect pseudouridine were introduced from classic mass spectrometry-based methods to newer approaches such as nanopore-based technologies and BID sequencing, each with its advantages and limitations.
RNA pseudouridylation is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre-mRNA splicing, enhancement of mRNA translation, and translational fidelity.
Increased pseudouridylation is frequently associated with tumour initiation, progression, and poor prognosis, whereas its reduction is predominantly implicated in non-tumour diseases.
A comprehensive understanding of the inducing factors for RNA pseudouridylation will be essential for elucidating its role in diseases. Such insights can provide robust evidence for how pseudouridylation influences disease progression and offer new avenues for therapeutic strategies targeting pseudouridylation dysregulation.
The therapeutic potential of RNA pseudouridylation in diseases is enormous, including inhibitors targeting pseudouridine synthases, the application of RNA pseudouridylation in RNA therapeutics, and its role as a biological marker.

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解读人类疾病中的假尿嘧啶核碱基修饰：从分子机制到临床观点。

RNA假尿嘧啶化是一种动态可逆的转录后修饰，存在于多种RNA物种中，对多种生物过程至关重要，包括tRNA稳态、tRNA转运、翻译起始调控、mRNA前剪接、mRNA翻译增强和翻译保真度。假尿嘧啶化的破坏会损害细胞稳态，导致病理改变。最近的研究强调了它在人类疾病，特别是肿瘤发生中的调节作用。细胞应激触发RNA假尿嘧啶化，提示假尿嘧啶化介导的表观遗传重编程对于维持细胞活力和应对应激至关重要。本文综述了假尿嘧啶化在人类疾病中的调控机制和病理意义，重点讨论了其在肿瘤发生中的作用。此外，它还探讨了靶向假尿嘧啶化的治疗潜力，为疾病治疗提供了新的策略。重点介绍了假尿嘧啶的检测方法，从经典的基于质谱的方法到基于纳米孔的技术和BID测序等新方法，每种方法都有其优点和局限性。RNA假尿嘧啶化对多种生物过程至关重要，包括tRNA稳态、tRNA转运、翻译起始调控、mRNA前剪接、mRNA翻译增强和翻译保真度。假尿嘧啶化增加通常与肿瘤的发生、进展和预后不良有关，而其减少主要与非肿瘤疾病有关。全面了解RNA假尿嘧啶化的诱导因子对于阐明其在疾病中的作用至关重要。这些见解可以为假尿嘧啶化如何影响疾病进展提供有力的证据，并为针对假尿嘧啶化失调的治疗策略提供新的途径。RNA假尿嘧啶化在疾病中的治疗潜力是巨大的，包括靶向假尿嘧啶合成酶的抑制剂，RNA假尿嘧啶化在RNA治疗中的应用，以及它作为生物标志物的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.