Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
Trends Genet. 2013 Feb;29(2):108-15. doi: 10.1016/j.tig.2012.11.003. Epub 2012 Dec 4.
N(6)-methyladenosine (m(6)A) is a ubiquitous modification in mRNA and other RNAs across most eukaryotes. For many years, however, the exact functions of m(6)A were not clearly understood. The discovery that the fat mass and obesity-associated protein (FTO) is an m(6)A demethylase indicates that this modification is reversible and dynamically regulated, suggesting that it has regulatory roles. In addition, it has been shown that m(6)A affects cell fate decisions in yeast and plant development. Recent affinity-based m(6)A profiling in mouse and human cells further showed that this modification is a widespread mark in coding and noncoding RNA (ncRNA) transcripts and is likely dynamically regulated throughout developmental processes. Therefore, reversible RNA methylation, analogous to reversible DNA and histone modifications, may affect gene expression and cell fate decisions by modulating multiple RNA-related cellular pathways, which potentially provides rapid responses to various cellular and environmental signals, including energy and nutrient availability in mammals.
N(6)-甲基腺苷(m(6)A)是真核生物中 mRNA 和其他 RNA 中普遍存在的一种修饰。然而，多年来，m(6)A 的确切功能并不清楚。脂肪量和肥胖相关蛋白(FTO)是 m(6)A 去甲基酶的发现表明这种修饰是可逆和动态调节的，这表明它具有调节作用。此外，已经表明 m(6)A 影响酵母和植物发育中的细胞命运决定。最近在小鼠和人类细胞中进行的基于亲和力的 m(6)A 分析进一步表明，这种修饰是编码和非编码 RNA(ncRNA)转录本中的一个广泛标记，并且可能在整个发育过程中动态调节。因此，类似于可逆的 DNA 和组蛋白修饰，RNA 甲基化的可逆性可能通过调节多个与 RNA 相关的细胞途径来影响基因表达和细胞命运决定，这可能为哺乳动物对各种细胞和环境信号(包括能量和营养供应)的快速反应提供了基础。
