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.