Division of Epigenetics, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
Bioessays. 2013 Dec;35(12):1044-9. doi: 10.1002/bies.201300088. Epub 2013 Sep 9.
Many species maintain cytosine DNA methyltransferase (MTase) genes belonging to the Dnmt2 family. Prokaryotic modification-restriction systems utilize DNA methylation to distinguish between self and foreign DNA, and cytosine methylation in eukaryotic DNA contributes to epigenetic mechanisms that control gene expression. However, Dnmt2 proteins display only low or no DNA MTase activity, making this protein family the odd and enigmatic family member. Recent evidence showed that Dnmt2 proteins are not DNA but RNA MTases with functions in biological processes as diverse as stress responses and RNA-mediated inheritance. These observations not only raise profound questions regarding the perceived substrate specificities of cytosine MTase, but also suggest links between DNA and RNA modification systems. Here, we speculate that Dnmt2 proteins might be part of an ancient cytosine modification toolbox that is used to successfully respond to environmental challenges, including constantly evolving RNA and DNA substrates.
许多物种都维持着属于 Dnmt2 家族的胞嘧啶 DNA 甲基转移酶（MTase）基因。原核修饰-限制系统利用 DNA 甲基化来区分自身和外源 DNA，而真核 DNA 中的胞嘧啶甲基化有助于控制基因表达的表观遗传机制。然而，Dnmt2 蛋白仅显示出低或无 DNA MTase 活性，使该蛋白家族成为奇怪而神秘的家族成员。最近的证据表明，Dnmt2 蛋白不是 DNA 而是 RNA MTases，在应激反应和 RNA 介导的遗传等多种生物学过程中发挥作用。这些观察结果不仅对被认为的胞嘧啶 MTase 的底物特异性提出了深刻的问题，而且还暗示了 DNA 和 RNA 修饰系统之间的联系。在这里，我们推测 Dnmt2 蛋白可能是一种古老的胞嘧啶修饰工具箱的一部分，该工具箱用于成功应对环境挑战，包括不断进化的 RNA 和 DNA 底物。
