Trends in Biochemical Sciences
Research FocusTwo substrates are better than one: dual specificities for Dnmt2 methyltransferases
Section snippets
Eukaryotic DNA methyltransferases
DNA methylation is important in organismal development and human disease 1, 2. In eukaryotes, there are three distinct families of DNA methyltransferases: Dnmt1, Dnmt2 and Dnmt3 [3]. Whereas Dnmt3 enzymes seem to be responsible for establishing DNA methylation patterns (de novo methyltransferases), Dnmt1 enzymes are involved in maintaining methylation patterns. By contrast, the biochemical activity and the biological function of Dnmt2 enzymes have remained enigmatic for a long time.
Dnmt2
Dnmt2 methylates tRNAAsp
In a recent biochemical study, Goll et al. [11] generated Dnmt2 knockouts in diverse model systems (mouse, Drosophila and Arabidopsis) to investigate the function of this enzyme. Using RNA preparations from these Dnmt2 mutants, they found that tRNAAsp is methylated with high efficiency by Dnmt2. Intriguingly, this modification seems to be highly specific, because they did not detect Dnmt2-dependent methylation of other RNA molecules. Detailed mass spectrometric analyses indicated that the
Functional characterization of Dnmt2 enzymes
Drosophila and Dictyostelium are especially well suited to functional studies because both organisms contain a single Dnmt2-like methyltransferase candidate gene; thus, their use avoids the need to differentiate experimentally among related enzymatic activities with potentially overlapping functions. In both organisms, the gene encoding Dnmt2 is differentially expressed during development, suggesting that it might have a regulatory function. The mutation or knockout of Dnmt2 in either organism
Evolution of eukaryotic DNA methyltransferases
On the basis of the tRNAAsp methyltransferase activity of Dnmt2, Goll et al. [11] have suggested that eukaryotic DNA methylation might have evolved from eukaryotic RNA methylation. This proposal contrasts with the prevailing concept that eukaryotic DNA methylation evolved from prokaryotic restriction modification systems [13] and will have to be validated in the future by phylogenetic analyses. In the absence of any data supporting this idea, it should be noted that a dual – DNA and RNA
Acknowledgements
We acknowledge financial support from the Deutsche Forschungsgemeinschaft (Priority Programme Epigenetics).
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