Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Wiley Interdiscip Rev RNA. 2020 Sep;11(5):e1595. doi: 10.1002/wrna.1595. Epub 2020 Apr 16.
The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as the "fifth" ribonucleotide in 1951. Since then, the ever-increasing number and complexity of modified ribonucleosides have been found in viruses and throughout all three domains of life. Such modifications can be as simple as methylations, hydroxylations, or thiolations, complex as ring closures, glycosylations, acylations, or aminoacylations, or unusual as the incorporation of selenium. While initially found in transfer and ribosomal RNAs, modifications also exist in messenger RNAs and noncoding RNAs. Modifications have profound cellular outcomes at various levels, such as altering RNA structure or being essential for cell survival or organism viability. The aberrant presence or absence of RNA modifications can lead to human disease, ranging from cancer to various metabolic and developmental illnesses such as Hoyeraal-Hreidarsson syndrome, Bowen-Conradi syndrome, or Williams-Beuren syndrome. In this review article, we summarize the characterization of all 143 currently known modified ribonucleosides by describing their taxonomic distributions, the enzymes that generate the modifications, and any implications in cellular processes, RNA structure, and disease. We also highlight areas of active research, such as specific RNAs that contain a particular type of modification as well as methodologies used to identify novel RNA modifications. This article is categorized under: RNA Processing > RNA Editing and Modification.
自 1951 年假尿嘧啶被描述为“第五个”核糖核苷酸以来，RNA 分子的化学特征就一直令科学家着迷。从那时起，越来越多的修饰核糖核苷酸在病毒以及生命的三个域中被发现。这些修饰可以像甲基化、羟化或硫代那样简单，也可以像环闭合、糖基化、酰化或氨酰化那样复杂，或者像硒的掺入那样不寻常。虽然最初在转移 RNA 和核糖体 RNA 中发现了修饰，但在信使 RNA 和非编码 RNA 中也存在修饰。修饰在各个层面都有深远的细胞后果，例如改变 RNA 结构或对细胞存活或生物体活力至关重要。RNA 修饰的异常存在或缺失可能导致人类疾病，从癌症到各种代谢和发育疾病，如 Hoyeraal-Hreidarsson 综合征、Bowen-Conradi 综合征或 Williams-Beuren 综合征。在这篇综述文章中，我们通过描述其分类分布、生成修饰的酶以及在细胞过程、RNA 结构和疾病中的任何影响，总结了所有 143 种已知修饰核糖核苷酸的特征。我们还强调了一些活跃的研究领域，例如含有特定类型修饰的特定 RNA 以及用于鉴定新的 RNA 修饰的方法。本文属于以下分类：RNA 加工 > RNA 编辑与修饰。
