Dynamic transcriptomic m5C and its regulatory role in RNA processing

• Published in: Wiley interdisciplinary reviews. RNA 2021-07, Vol.12 (4), p.e1639-n/a
• Main Authors: Chen, Yu‐Sheng, Yang, Wen‐Lan, Zhao, Yong‐Liang, Yang, Yun‐Gui
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; 5' Untranslated Regions; 5‐methylcytosine; Cell migration; Embryogenesis; epitranscriptome; Eukaryotes; Frustration; Gametogenesis; Mitochondria; mRNA; mRNA stability; ncRNA; Prokaryotes; Regulatory sequences; RNA editing; RNA modification; RNA processing; RNA transport; Transcriptomics; Tumorigenesis
• ISSN: 1757-7004; 1757-7012
• DOI: 10.1002/wrna.1639

RNA 5‐methylcytosine (m5C) is a prevalent RNA modification in multiple RNA species, including messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), and noncoding RNAs (ncRNAs), and broadly distributed from archaea, prokaryotes to eukaryotes. The multiple detecting techniques of m5C have been developed, such as m5C‐RIP‐seq, miCLIP‐seq, AZA‐IP‐seq, RNA‐BisSeq, TAWO‐seq, and Nanopore sequencing. These high‐throughput techniques, combined with corresponding analysis pipeline, provide a precise m5C landscape contributing to the deciphering of its biological functions. The m5C modification is distributed along with mRNA and enriched around 5′UTR and 3′UTR, and conserved in tRNAs and rRNAs. It is dynamically regulated by its related enzymes, including methyltransferases (NSUN, DNMT, and TRDMT family members), demethylases (TET families and ALKBH1), and binding proteins (ALYREF and YBX1). So far, accumulative studies have revealed that m5C participates in a variety of RNA metabolism, including mRNA export, RNA stability, and translation. Depletion of m5C modification in the organism could cause dysfunction of mitochondria, drawback of stress response, frustration of gametogenesis and embryogenesis, abnormality of neuro and brain development, and has been implicated in cell migration and tumorigenesis. In this review, we provide a comprehensive summary of dynamic regulatory elements of RNA m5C, including methyltransferases (writers), demethylases (erasers), and binding proteins (readers). We also summarized the related detecting technologies and biological functions of the RNA 5‐methylcytosine, and provided future perspectives in m5C research. This article is categorized under: RNA Processing > RNA Editing and Modification High‐throughput sequencing technologies reveal that RNA 5‐methylcytosine plays dynamic regulatory roles in the diverse cellular processes via its writer, eraser, and reader.