Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism

Jurkowski, Tomasz P ORCID: https://orcid.org/0000-0002-2012-0240, Meusburger, Madeleine, Phalke, Sameer, Helm, Mark, Nellen, Wolfgang, Reuter, Gunter and Jeltsch, Albert 2008. Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA 14 (8) , 1663—1670. 10.1261/rna.970408

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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 tRNAAsp. 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 tRNAAsp 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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences
Publisher:	Cold Spring Harbor Laboratory Press: 12 month Embargo
ISSN:	1355-8382
Date of Acceptance:	17 April 2008
Last Modified:	25 Oct 2022 13:08
URI:	https://orca.cardiff.ac.uk/id/eprint/118982

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