Department of Life Sciences and Medicine, University of Luxembourg, L-4367 Belvaux, Luxembourg.
CNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), 70126 Bari, Italy.
Int J Mol Sci. 2020 Jun 30;21(13):4684. doi: 10.3390/ijms21134684.
In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed "epitranscriptomics", in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome's characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications ("stages") until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.
在过去的几年中，对核糖核酸（RNA）分子在细胞中进行的化学修饰的深入研究正在兴起。这个新的研究领域被称为“表观转录组学”，与广为人知的表观基因组学类似，以强调 RNA 修饰的集合有可能构成由 RNA 结合蛋白（RBPs）的“写入器”、“读取器”和“擦除器”组成的转录后基因表达调控层。事实上，表观转录组学旨在识别和描述涉及非替代化学修饰和编辑事件的所有功能相关变化，这些变化发生在转录组中。事实上，迄今为止，在不同细胞 RNA 种类中，包括核糖体 RNA、转移 RNA、小核 RNA、信使 RNA 和长非编码 RNA 中，已经报道了几种影响基因表达的 RNA 修饰类型。支持这种尚未完全了解的调控机制的功能相关性，几种人类疾病已经直接与 RNA 修饰或可能作为表观转录组标记效应物的 RBPs 相关联。然而，全面描述表观转录组，旨在系统分类所有 RNA 修饰，并阐明这种有前途的调控密码的规则、参与者和结果，目前还不可用，主要受到缺乏合适检测技术的限制。这是一个不幸的局限性，由于特别是在测序技术领域的技术进步前所未有的步伐，这个局限性很可能很快就会被克服。在这里，我们回顾了关于表观转录组标记的现有知识，并提出了一种基于参考核苷酸及其修饰轮数（“阶段”）的分类方法，直到达到给定的修饰形式。我们相信，这种分类方案可以有助于一致地组织不断增加的已发现的 RNA 修饰。
