高等学校化学学报 ›› 2023, Vol. 44 ›› Issue (3): 20220340.doi: 10.7503/cjcu20220340

• 综合评述 • 上一篇    下一篇

化学干预N6-甲基腺嘌呤修饰的研究进展

郇歆宇, 赖淦强, 黄悦, 杨财广()   

  1. 中国科学院上海药物研究所, 上海 201203
  • 收稿日期:2022-05-14 出版日期:2023-03-10 发布日期:2023-03-14
  • 通讯作者: 杨财广 E-mail:yangcg@simm.ac.cn
  • 基金资助:
    国家杰出青年科学基金(21725801)

Research Progress on Chemical Intervention of N6-Methyladenosine Modification

HUAN Xinyu, LAI Ganqiang, HUANG Yue, YANG Caiguang()   

  1. Shanghai Institute of Material Medical,Chinese Academy of Sciences,Shanghai 201203,China
  • Received:2022-05-14 Online:2023-03-10 Published:2023-03-14
  • Contact: YANG Caiguang E-mail:yangcg@simm.ac.cn
  • Supported by:
    the National Science Fund for Distinguished Young Scholars, China(21725801)

摘要:

信使RNA(Messenger RNA, mRNA)上存在众多修饰, 包括N6-甲基腺嘌呤修饰(N6-methyladenosine, m6A)、 N1-甲基腺嘌呤修饰(N1-methyladenosine, m1A)及胞嘧啶甲基化(5-methylcytosine, m5C)等. 其中, m6A是mRNA内部修饰碱基中占比最高的一种, 影响着mRNA的5′和3′端加工、 在细胞中的定位、 降解和翻译等过程, 并在转录后调控基因表达水平, 以此参与胞内的多种生理活动. 本文综合评述了m6A修饰的分子机制及其与多种疾病的关系, 概述了m6A鉴定技术的发展历程, 重点讨论了m6A化学干预的最新研究进展, 以期让读者全面了解m6A修饰, 并为后续开发针对m6A修饰的小分子药物提供参考.

关键词: N6-甲基腺嘌呤修饰, 甲基转移酶, 去甲基化酶, 小分子抑制剂, 小分子激动剂

Abstract:

There are multiple modifications on mRNA, which includes N6-methyladenosine(m6A), N1-methyladenosine(m1A), 5-methylcytosine(m5C), etc. As the most common modification on mRNA, m6A has an impact on the processing of the 5′ ends and 3′ ends of mRNA, as well as the procedure of localization, degradation, and translation. It also regulates the expression of genes at the post-transcriptional level and participates in manifold physiological activities. This paper made a review of the mechanisms on the molecular level of the m6A modification and the relationship between the modification and various diseases. Then it outlined the development course of the m6A identification technology, emphasized on the latest research progress on m6A chemical intervention in order to enable the readers to form a comprehensive understanding of m6A modification and provide references for the development of small-molecular drugs targeting on m6A modification.

Key words: N6-Methyladenosine modification, Methyltransferase, Demethylase, Small molecule inhibitor, Small molecule agonist

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