Abstract：
Cellular RNAs, both coding and noncoding are adorned by > 100 chemical modifications, which impact various facets of RNA metabolism and gene expression. Very often derailments in these modifications are associated with a plethora of human diseases. One of the most oldest of such modification is pseudouridylation of RNA, wherein uridine is converted to a pseudouridine (Ψ) via an isomerization reaction. When discovered, Ψ was referred to as the \'fifth nucleotide\' and is chemically distinct from uridine and any other known nucleotides. Experimental evidence accumulated over the past six decades, coupled together with the recent technological advances in pseudouridine detection, suggest the presence of pseudouridine on messenger RNA, as well as on diverse classes of non-coding RNA in human cells. RNA pseudouridylation has widespread effects on cellular RNA metabolism and gene expression, primarily via stabilizing RNA conformations and destabilizing interactions with RNA-binding proteins. However, much remains to be understood about the RNA targets and their recognition by the pseudouridylation machinery, the regulation of RNA pseudouridylation, and its crosstalk with other RNA modifications and gene regulatory processes. In this review, we summarize the mechanism and molecular machinery involved in depositing pseudouridine on target RNAs, molecular functions of RNA pseudouridylation, tools to detect pseudouridines, the role of RNA pseudouridylation in human diseases like cancer, and finally, the potential of pseudouridine to serve as a biomarker and as an attractive therapeutic target.
摘要：
细胞RNA，编码和非编码都被>100个化学修饰所装饰，影响RNA代谢和基因表达的各个方面。这些修饰中的脱轨通常与过多的人类疾病有关。这种修饰中最古老的修饰之一是RNA的假尿苷化，其中尿苷通过异构化反应转化为假尿苷(Φ)。当被发现时,Φ被称为“第五核苷酸”，在化学上与尿苷和任何其他已知的核苷酸不同。过去六十年积累的实验证据，再加上最近伪尿苷检测的技术进步，表明信使RNA上存在假尿苷，以及人类细胞中不同类别的非编码RNA。RNA假尿酰对细胞RNA代谢和基因表达有广泛的影响,主要通过稳定RNA构象和与RNA结合蛋白的不稳定相互作用。然而,关于RNA靶标及其通过伪吡啶化机制的识别还有很多有待理解，RNA假尿嘧啶化的调控，以及它与其他RNA修饰和基因调控过程的串扰。在这次审查中,我们总结了假尿苷在靶RNA上沉积的机制和分子机制，RNA假尿苷化的分子功能，检测伪尿嘧啶的工具，在人类疾病如癌症中，RNA假尿嘧啶化的作用，最后，假尿苷作为生物标志物和有吸引力的治疗靶点的潜力。
