Jia Shiheng, Yu Xue, Deng Na, Zheng Chen, Ju Mingguang, Wang Fanglin, Zhang Yixiao, Gao Ziming, Li Yanshu, Zhou Heng, Li Kai
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Hematology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Clin Transl Med. 2025 Jan;15(1):e70190. doi: 10.1002/ctm2.70190.
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.
RNA假尿苷化是一种在多种RNA种类中发现的动态且可逆的转录后修饰，对各种生物学过程至关重要，包括tRNA稳态、tRNA转运、翻译起始调控、前体mRNA剪接、mRNA翻译增强以及翻译保真度。假尿苷化的破坏会损害细胞稳态，导致病理改变。最近的研究突出了其在人类疾病，特别是肿瘤发生中的调节作用。细胞应激会触发生物体中的RNA假尿苷化，这表明假尿苷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。本综述探讨了假尿苷化在人类疾病中的调节机制和病理意义，重点关注其在肿瘤发生中的作用。此外，还探讨了靶向假尿苷化的治疗潜力，提出了疾病治疗的新策略。要点：检测假尿苷的方法从基于经典质谱的方法介绍到了更新的方法，如基于纳米孔的技术和BID测序，每种方法都有其优缺点。RNA假尿苷化对各种生物学过程至关重要，包括tRNA稳态、tRNA转运、翻译起始调控、前体mRNA剪接、mRNA翻译增强以及翻译保真度。假尿苷化增加通常与肿瘤起始、进展和不良预后相关，而其减少主要与非肿瘤疾病有关。全面了解RNA假尿苷化的诱导因素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苷化如何影响疾病进展提供有力证据，并为针对假尿苷化失调的治疗策略提供新途径。RNA假尿苷化在疾病中的治疗潜力巨大，包括靶向假尿苷合酶的抑制剂、RNA假尿苷化在RNA治疗中的应用以及其作为生物标志物的作用。
