Goll Mary Grace, Kirpekar Finn, Maggert Keith A, Yoder Jeffrey A, Hsieh Chih-Lin, Zhang Xiaoyu, Golic Kent G, Jacobsen Steven E, Bestor Timothy H
Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Science. 2006 Jan 20;311(5759):395-8. doi: 10.1126/science.1120976.
The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNA(Asp)) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNA(Asp) from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila melanogaster in a manner that was dependent on preexisting patterns of modified nucleosides. Indirect sequence recognition is also a feature of eukaryotic DNA methyltransferases, which may have arisen from a Dnmt2-like RNA methyltransferase.
DNA甲基转移酶2（Dnmt2）的序列和结构与真正的DNA胞嘧啶甲基转移酶密切相关。综合遗传学和生物化学方法表明，人类DNMT2并不使DNA甲基化，而是使一种小RNA甲基化；质谱分析显示，这种RNA是天冬氨酸转运RNA（tRNA（Asp）），并且DNMT2特异性地使反密码子环中的胞嘧啶38甲基化。DNMT2的功能高度保守，人类DNMT2蛋白在体外以依赖于修饰核苷的现有模式的方式，将来自小鼠、拟南芥和果蝇的Dnmt2缺陷菌株的tRNA（Asp）恢复甲基化。间接序列识别也是真核DNA甲基转移酶的一个特征，这可能源于一种类似Dnmt2的RNA甲基转移酶。
