Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism |
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| Authors: | Jurkowski Tomasz P Meusburger Madeleine Phalke Sameer Helm Mark Nellen Wolfgang Reuter Gunter Jeltsch Albert |
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| Affiliation: | Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany. |
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| Abstract: | Although their amino acid sequences and structure closely resemble DNA methyltransferases, Dnmt2 proteins were recently shown by Goll and colleagues to function as RNA methyltransferases transferring a methyl group to the C5 position of C38 in tRNA(Asp). We observe that human DNMT2 methylates tRNA isolated from Dnmt2 knock-out Drosophila melanogaster and Dictyostelium discoideum. RNA extracted from wild type D. melanogaster was methylated to a lower degree, but in the case of Dictyostelium, there was no difference in the methylation of RNA isolated from wild-type and Dnmt2 knock-out strains. Methylation of in vitro transcribed tRNA(Asp) confirms it to be a target of DNMT2. Using site directed mutagenesis, we show here that the enzyme has a DNA methyltransferase-like mechanism, because similar residues from motifs IV, VI, and VIII are involved in catalysis as identified in DNA methyltransferases. In addition, exchange of C292, which is located in a CFT motif conserved among Dnmt2 proteins, strongly reduced the catalytic activity of DNMT2. Dnmt2 represents the first example of an RNA methyltransferase using a DNA methyltransferase type of mechanism. |
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| Keywords: | Dnmt2 catalytic mechanism RNA methylation tRNAAsp |
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