Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Trends Biochem Sci. 2013 Apr;38(4):204-9. doi: 10.1016/j.tibs.2012.12.006. Epub 2013 Jan 19.
N6-methyl-adenosine (m(6)A) is the most abundant modification in mammalian mRNA and long non-coding RNA. First discovered in the 1970s, m(6)A modification has been proposed to function in mRNA splicing, export, stability, and immune tolerance. Interest and excitement in m(6)A modification has recently been revived based on the discovery of a mammalian enzyme that removes m(6)A and the application of deep sequencing to localize modification sites. The m(6)A demethylase fat mass and obesity associated protein (FTO) controls cellular energy homeostasis and is the first enzyme discovered that reverses an RNA modification. m(6)A Sequencing demonstrates cell-type- and cell-state-dependent m(6)A patterns, indicating that m(6)A modifications are highly regulated. This review describes the current knowledge of mammalian m(6)A modifications and future perspectives on how to push the field forward.
N6-甲基腺苷(m(6)A)是哺乳动物 mRNA 和长非编码 RNA 中最丰富的修饰。m(6)A 修饰于 20 世纪 70 年代首次被发现,据推测其功能在于 mRNA 的剪接、输出、稳定性和免疫耐受。基于对一种能去除 m(6)A 的哺乳动物酶的发现,以及对修饰位点进行定位的深度测序技术的应用,m(6)A 修饰最近又重新引起了人们的兴趣和关注。肥胖相关蛋白(FTO)是一种脂肪质量和肥胖相关蛋白,它控制着细胞的能量稳态,是发现的第一种能逆转 RNA 修饰的酶。m(6)A 测序表明 m(6)A 模式具有细胞类型和细胞状态依赖性,这表明 m(6)A 修饰受到高度调控。本综述描述了目前对哺乳动物 m(6)A 修饰的认识,以及推动该领域发展的未来展望。