Mo Jing, Weng Xiaocheng, Zhou Xiang
College of Chemistry and Molecular Sciences, Department of Clinical Laboratory of Zhongnan Hospital, Department of Hematology of Zhongnan Hospital, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, China.
Acc Chem Res. 2023 Oct 17;56(20):2788-2800. doi: 10.1021/acs.accounts.3c00395. Epub 2023 Sep 28.
ConspectusWith increasing research interest, more than 170 types of chemical modifications of RNA have been characterized. The epigenetic modifications of RNA do not alter the primary sequence of RNA but modulate the gene activity. Increasing numbers of regulatory functions of these RNA modifications, particularly in controlling mRNA fate and gene expression, are being discovered. To gain a deeper understanding of the biological significance and clinical prospects of RNA modifications, the development of innovative labeling and detection methodologies is of great importance. Owing to the dynamic features of RNA modifications and the fact that only a portion of genes are modified, detection methods should accurately reveal the precise distribution and modification level of RNA modifications. In general, detection methodologies identify specific RNA modifications in two ways: (1) enriching modification-containing RNAs; and (2) altering the Watson-Crick base pairing pattern to produce truncation or mutation signatures. Additionally, it is important to develop flexible and accurate manipulation tools that enable the installation or removal of RNA modifications at specific positions to investigate the biological functions of a single site. With the development of detection and manipulation methods, the scientific understanding of the biological functions of RNA modifications has increased, paving the way for applications of RNA modifications in disease diagnosis and treatments.In this Account, we provide a brief summary of recent efforts to develop methodologies for detecting RNA modifications. Through the evolution of these detection techniques, our team has uncovered the potential biological roles of RNA modifications in diseases such as diabetic cardiovascular complications, viral infections, and hematologic malignancies. We mainly summarize the recently developed strategies for manipulating RNA modifications. The advent of these programmable editing tools allows for the precise installation or removal of RNA modifications at specific positions. As a result, the biological functions of RNA modifications at these specific loci could be identified, further advancing our knowledge in this field.With this Account, we anticipate providing chemical and biological researchers with comprehensive strategies to discover the underlying mechanisms of RNA modification-mediated biological processes. Although the field of RNA modifications has undergone rapid progress in recent years, our understanding of most of these RNA modifications remains incomplete. We hope to inspire efforts to expand the toolbox for investigating RNA modifications and promote translational research on epigenetics in clinical diagnosis and treatment.
概述
随着研究兴趣的增加，已鉴定出170多种RNA的化学修饰类型。RNA的表观遗传修饰不会改变RNA的一级序列，但会调节基因活性。这些RNA修饰的调控功能越来越多，特别是在控制mRNA命运和基因表达方面。为了更深入地了解RNA修饰的生物学意义和临床前景，开发创新的标记和检测方法至关重要。由于RNA修饰的动态特性以及只有一部分基因被修饰这一事实，检测方法应准确揭示RNA修饰的精确分布和修饰水平。一般来说，检测方法通过两种方式识别特定的RNA修饰：（1）富集含有修饰的RNA；（2）改变沃森-克里克碱基配对模式以产生截断或突变特征。此外，开发灵活且准确的操作工具也很重要，这些工具能够在特定位置安装或去除RNA修饰，以研究单个位点的生物学功能。随着检测和操作方法的发展，对RNA修饰生物学功能的科学认识有所增加，为RNA修饰在疾病诊断和治疗中的应用铺平了道路。
在本综述中，我们简要总结了近期开发RNA修饰检测方法的努力。通过这些检测技术的发展，我们的团队发现了RNA修饰在糖尿病心血管并发症、病毒感染和血液系统恶性肿瘤等疾病中的潜在生物学作用。我们主要总结了近期开发的操纵RNA修饰的策略。这些可编程编辑工具的出现使得能够在特定位置精确安装或去除RNA修饰。因此，可以确定这些特定位点的RNA修饰的生物学功能，进一步推动我们在该领域的知识发展。
通过本综述，我们期望为化学和生物学研究人员提供全面的策略，以发现RNA修饰介导的生物学过程的潜在机制。尽管RNA修饰领域近年来取得了快速进展，但我们对大多数这些RNA修饰的理解仍然不完整。我们希望激发人们努力扩展研究RNA修饰的工具库，并促进表观遗传学在临床诊断和治疗中的转化研究。
