Emerging Roles of RNA Methylation in Development

Abstract

Conspectus More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N 6 -methyladenine (m 6 A), 5-methylcytosine (m 5 C), N 1 -methyladenine (m 1 A), and N 7 -methylguanosine (m 7 G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples. This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m 6 A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m 5 C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m 1 A, with a lower abundance than m 6 A, is widely distributed in various RNA types, mainly locates in the 5′ untranslated region (5′UTR) of mRNA and regulates translation. RNA m 7 G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention. Thanks to the development of sequencing technology, m 6 A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m 5 C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m 5 C dependent manner. m 1 A also has been revealed to be involved in these developmental processes. m 7 G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases. Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.