N6-methyl-adenosine (m6A) in RNA: an old modification with a novel epigenetic function.
N6-methyl-adenosine (m6A) in RNA: an old modification with a novel epigenetic function.
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RNA 中的 N6-甲基-腺苷 (m6A)：具有新表观遗传功能的旧修饰
DOI：
10.1016/j.gpb.2012.12.002
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发表时间：
2013-02
影响因子：
9.5
通讯作者：
Yang, Yun-Gui
中科院分区：
文献类型：
--
作者：
Niu, Yamei;Zhao, Xu;Wu, Yong-Sheng;Li, Ming-Ming;Wang, Xiu-Jie;Yang, Yun-Gui
N6-甲基腺苷（m6 A）是真核生物中最常见和最丰富的RNA分子修饰之一。然而，m6 A甲基化的生物学意义在很大程度上仍然未知。一些独立的证据表明，m6 A的动态调节可能对基因表达调控产生深远的影响。m6 A修饰由一种未鉴定的甲基转移酶复合物催化，该复合物含有至少一个亚基甲基转移酶样3（stomach L3）。高通量m6 A-seq分析表明，m6 A对mRNA的修饰主要发生在外显子区和3′-非翻译区（3′-UTR）。m6 A研究的一个重要进展是最近发现了前两个m6 A RNA去甲基化酶脂肪质量和肥胖相关（FTO）基因和ALKBH 5，它们以α-酮戊二酸（α-KG）和Fe 2+依赖的方式催化m6 A去甲基化。最近在模式生物中的研究表明，胃L3，FTO和ALKBH 5在许多生物过程中发挥重要作用，从发育和代谢到生育。此外，这些酶的活性的扰动导致在细胞水平上的数千个基因的表达受到干扰，暗示了m6 A在RNA代谢中的调节作用。鉴于DNA和组蛋白甲基化在哺乳动物基本生命过程的表观遗传调控中的重要作用，RNA上的动态和可逆的化学m6 A修饰也可以作为具有深刻生物学意义的新的表观遗传标记。
N6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3′-untranslated region (3′-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.
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