RNA甲基化修饰调控和规律

RNA methylation: regulations and mechanisms

表观遗传学修饰包括DNA、RNA和蛋白质的化学修饰,基于非序列改变所致基因表达和功能水平变化。近年来,在DNA和蛋白质修饰基础上,可逆RNA甲基化修饰研究引领了第3次表观遗传学修饰研究的浪潮。RNA存在100余种化学修饰,甲基化是最主要的修饰形式。鉴定RNA甲基化修饰酶及研发其转录组水平高通量检测技术,是揭示RNA化学修饰调控基因表达和功能规律的基础。本文主要总结了近年来本课题组与合作团队及国内外同行在RNA甲基化表观转录组学研究中取得的主要前沿进展,包括发现了RNA去甲基酶、甲基转移酶和结合蛋白,揭示RNA甲基化修饰调控RNA加工代谢,及其调控正常生理和异常病理等重要生命进程。这些系列研究成果证明RNA甲基化修饰类似于DNA甲基化,具有可逆性,拓展了RNA甲基化表观转录组学研究新领域,完善了中心法则表观遗传学规律。

Epigenetic modifications include the chemical modifications on DNA,RNA and proteins characterized by altered gene expression and function without any changes in the gene sequence.In addition to well-established DNA and protein epigenetic modifications,the reversible RNA methylation has led the third wave of studies in the epigenetic field.RNA has more than 100 chemical modifications,among which methylation is the major type.The identification of catalyzing enzymes for RNA methylation and the development of high-throughput detection technologies for RNA modification at the transcriptomic level are the prerequisites for revealing the regulatory role of RNA methylation in gene expression and biological functions.In this review,we summarize the recent frontier in RNA methylation-mediated epitranscriptomics from our and other laboratories,with emphasis on the discoveries of RNA modification demethylase,methyltransferase and binding protein as well as the illustration of regulatory roles of RNA methylation modification in hematopoietic stem cell differentiation,spermatogenesis,brain development and other pivotal life processes.These findings have shown that RNA methylation is just as reversible as DNA methylation,and opened up a novel field in RNA methylation-mediated epitranscriptomics,which appends a new layer of epigenetic regulation to the central genetic dogma.