Liu Kaijie, Zhang Shujun, Liu Yafeng, Hu Xinjun, Gu Xinyu
Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China.
Henan Medical Key Laboratory of Gastrointestinal Microecology and Hepatology, Luoyang, China.
Front Cell Dev Biol. 2024 Dec 16;12:1465546. doi: 10.3389/fcell.2024.1465546. eCollection 2024.
Pseudouridine (Ψ) is a post-transcriptional modifier of RNA, often referred to as the 'fifth nucleotide' owing to its regulatory role in various biological functions as well as because of its significant involvement in the pathogenesis of human cancer. In recent years, research has revealed various Ψ modifications in different RNA types, including messenger RNA, transfer RNA, ribosomal RNA, small nuclear RNA, and long noncoding RNA. Pseudouridylation can significantly alter RNA structure and thermodynamic stability, as the Ψ-adenine (A) base pair is more stable than the typical uridine (U)-A base pair is due to its structural similarity to adenine. Studies have linked Ψ expression to the development and progression of several digestive system cancers, such as liver cancer and colorectal cancer, and nondigestive system cancers, such as breast cancer, non-small cell lung cancer, prostate cancer, glioblastoma, ovarian cancer, oral squamous cell carcinoma, and pituitary cancer. The present review briefly outlines the chemical structure, synthesis, and regulatory mechanisms of Ψ. This review summarizes the effects of pseudouridylation on various substrates of RNA and briefly discusses methods for detecting Ψ. Last, it focuses on how RNA pseudouridylation influences different cancers, emphasizing the search for novel approaches to cancer diagnosis, treatment, and prognosis through Ψ modification.
假尿苷(Ψ)是RNA的一种转录后修饰物,由于其在多种生物学功能中的调节作用以及在人类癌症发病机制中的重要参与,常被称为“第五种核苷酸”。近年来,研究揭示了不同RNA类型中的各种Ψ修饰,包括信使RNA、转运RNA、核糖体RNA、小核RNA和长链非编码RNA。假尿苷化可显著改变RNA结构和热力学稳定性,因为Ψ-腺嘌呤(A)碱基对比典型的尿苷(U)-A碱基对更稳定,这是由于其与腺嘌呤的结构相似性。研究已将Ψ的表达与几种消化系统癌症(如肝癌和结直肠癌)以及非消化系统癌症(如乳腺癌、非小细胞肺癌、前列腺癌、胶质母细胞瘤、卵巢癌、口腔鳞状细胞癌和垂体癌)的发生和发展联系起来。本综述简要概述了Ψ的化学结构、合成及调控机制。本综述总结了假尿苷化对RNA各种底物的影响,并简要讨论了检测Ψ的方法。最后,重点阐述了RNA假尿苷化如何影响不同癌症,强调通过Ψ修饰寻找癌症诊断、治疗和预后的新方法。