N6-methyladenosine (m6A) is prevalent in eukaryotic cells and is the most abundant mRNA modifications. With the development and advances of technologies for detecting m6A, distributions and functions of m6A modification have been widely investigated in the past decade; extensive studies had demonstrated the vital functions of m6A in various biological conditions, including embryonic development, physiological metabolism, circadian rhythm, stimulation response, pathogenesis, and etc.
Unlike DNA methylation which is relatively stable, m6A modification on mRNA is more dynamic, and is more rapidly influenced by various internal and external factors. Therefore, deciphering the mechanisms governing m6A dynamics and selectivity is of great importance for understanding the epi-transcriptomic regulation of various biological processes.
Professor WANG Xiu-Jie of Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and her research team have been dedicated in studying the dynamic regulation of m6A in the past decade, and had made a series of high impact discoveries (Figure 1).
Figure 1. miRNAs guide m6A formation (left) and m6A regulates cerebellum development and long-term memory formation efficacy (right). (Image by IGDB)
Invited by Accounts of Chemical Research journal, Prof. WANG recently published a review article entitled with “N6-Methyladenosine mRNA Modification: From Modification Site Selectivity to Neurological Functions” to summarize findings made by her lab.
Based on the previous research experience of miRNA biology, Prof. WANG’s team and their collaborators worked together and for the first time uncovered m6A site selectivity was mediated by miRNA sequence pairing that miRNAs could guide m6A writer binding and m6A formation specifically on their target mRNAs. Up- or down-regulation of miRNAs in cells could increase or decrease m6A abundance on their target mRNAs, respectively; moreover, introducing artificially designed miRNA sequence into cells could even ab initio create new m6A sites.
Following this finding, Prof. WANG and her team continued to study the physiological functions of m6A in brain development and memory formation, and uncovered m6A regulated cerebellum development by controlling the proper transcription, splicing and turnover of key genes involved in neural differentiation. In addition, they were also the first team that revealed m6A promoted the efficacy of long-term memory formation by upregulating the translation of learning-induced immediate early genes. Though mice with different levels of brain m6A formed long-term memory with different speed, such difference could be compensated by adequate training, thus, their discovery also demonstrated the biological mechanisms of a Chinese proverb “diligence can make up dullness”.
This review also emphasized the importance of m6A site selectivity and its dynamics in regulating cell stress response, and discussed future directions of RNA modification study in depth.
This review and related works were supported by National Key Research and Development Program of China, Beijing Natural Science Foundation, and Chinese Academy of Sciences.
Contact: Professor WANG Xiu-Jie
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
CAS
中文
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Figure 1. miRNAs guide m6A formation (left) and m6A regulates cerebellum development and long-term memory formation efficacy (right). (Image by IGDB)Invited by Accounts of Chemical Research journal, Prof. WANG recently published a review article entitled with “N6-Methyladenosine mRNA Modification: From Modification Site Selectivity to Neurological Functions” to summarize findings made by her lab.Based on the previous research experience of miRNA biology, Prof. WANG’s team and their collaborators worked together and for the first time uncovered m6A site selectivity was mediated by miRNA sequence pairing that miRNAs could guide m6A writer binding and m6A formation specifically on their target mRNAs. Up- or down-regulation of miRNAs in cells could increase or decrease m6A abundance on their target mRNAs, respectively; moreover, introducing artificially designed miRNA sequence into cells could even ab initio create new m6A sites.Following this finding, Prof. WANG and her team continued to study the physiological functions of m6A in brain development and memory formation, and uncovered m6A regulated cerebellum development by controlling the proper transcription, splicing and turnover of key genes involved in neural differentiation. In addition, they were also the first team that revealed m6A promoted the efficacy of long-term memory formation by upregulating the translation of learning-induced immediate early genes. Though mice with different levels of brain m6A formed long-term memory with different speed, such difference could be compensated by adequate training, thus, their discovery also demonstrated the biological mechanisms of a Chinese proverb “diligence can make up dullness”.This review also emphasized the importance of m6A site selectivity and its dynamics in regulating cell stress response, and discussed future directions of RNA modification study in depth.This review and related works were supported by National Key Research and Development Program of China, Beijing Natural Science Foundation, and Chinese Academy of Sciences.Article link: https://pubs.acs.org/doi/10.1021/acs.accounts.3c00440Contact: Professor WANG Xiu-JieInstitute of Genetics and Developmental Biology, Chinese Academy of SciencesE-mail: xjwang@genetics.ac.cn