Similar to DNA and histone, RNA can also be methylated. In its most common form, a N6-methyladenosine (m 6 A) chemical modification is introduced into nascent messenger ribonucleic acid (mRNA) by a specialized methyltransferase complex and removed by the RNA demethylases, Fat mass and obesity-associated (FTO), and ALKBH5. The fate of m 6 A-marked mRNA is uniquely diverse, ranging from degradation to stabilization/translation, which has been suggested to be largely dependent on its interaction with the family of YT521-B homology (YTH) domain-containing proteins. Here, we highlight a series of control levers that impinge on the RNA demethylases. We present evidence to indicate that intermediary metabolism and various posttranslation modifications modulate the activity, stability, and the subcellular localization of FTO and ALKBH5, further dispelling the notion that m 6 A methylation is not a dynamic process. We also discuss how examination of these underappreciated regulatory nodes adds a more nuanced view of the role of FTO and ALKBH5 and should guide their study in cancer and nonmalignant conditions alike.

中文翻译：

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m 6 A RNA 去甲基化酶活性的动态多层控制


与 DNA 和组蛋白类似，RNA 也可以甲基化。在最常见的形式中，N6-甲基腺苷 （m 6 A） 化学修饰通过专门的甲基转移酶复合物引入新生的信使核糖核酸 （mRNA） 中，并被 RNA 去甲基化酶、脂肪量和肥胖相关 （FTO） 以及 ALKBH5 去除。m 6 A 标记的 mRNA 的命运是独特的多种多样的，从降解到稳定/翻译，这被认为在很大程度上取决于它与包含 YT521-B 同源 （YTH） 结构域的蛋白家族的相互作用。在这里，我们重点介绍了一系列影响 RNA 去甲基化酶的控制杠杆。我们提供的证据表明，中间代谢和各种翻译后修饰调节 FTO 和 ALKBH5 的活性、稳定性和亚细胞定位，进一步消除了 m 6 A 甲基化不是一个动态过程的概念。我们还讨论了对这些被低估的调节节点的检查如何增加对 FTO 和 ALKBH5 作用的更细致入微的看法，并应指导他们在癌症和非恶性疾病中的研究。