真核生物mRNA上的修饰核苷及在发育调控中的作用

Modified nucleosides in eukaryotic messenger RNAs and their roles in developmental regulation

信使RNA (Messenger RNA,mRNA)上的表观修饰对于转录本的稳定性和翻译活性有重要影响。在不同生物体的不同发育时期和不同组织器官中,特异转录本不同位点存在的核苷修饰影响mRNA的前体剪切、成熟mRNA的稳定性以及其翻译为蛋白质的效率。目前已知的170多种修饰核苷中在mRNA上发现的只占极少数,由于mRNA的丰度低、组织和发育特异性强等特点,研究mRNA特异位点的核苷修饰有很大的技术难度。近些年随着meRIP等技术的进步,mRNA核苷修饰功能的研究得到了长足的发展,特别是针对m6A、m5C等甲基化修饰的研究已经相当深入。文中简要回顾近年来mRNA核苷修饰领域的研究进展,对不同位点和不同类型的修饰核苷在不同物种生长发育中的调控作一总结,并对未来的研究热点和技术瓶颈展开讨论。

Epigenetic nucleoside modifications are critical for the stability and translational efficiency of messenger RNA. Depending on the organism, developmental stage, and tissue/organ investigated, the location and abundance of these nucleoside modifications may differ, which in turn influence the splicing event, half-life time of mature mRNA, as well as translation efficiency. Among the approximately 170 RNA nucleoside modifications, only a handful are found in mRNAs. The low abundance and high organ specificity make it a challenging work to study the role of each specific mRNA nucleoside modification. However, with the technical advances in recent years, including meRIP, great progress has been achieved, especially on the function of m6A and m5C epigenetic markers in eukaryotes. This review summarizes recent progress on nucleoside modifications of messenger RNAs, on their distribution on transcripts and their role in regulating growth and development. We also discuss the technical bottleneck and key issues for future investigation.