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The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA

Kaiser, Steffen, Jurkowski, Tomasz P, Kellner, Stefanie, Schneider, Dirk, Jeltsch, Albert and Helm, Mark 2017. The RNA methyltransferase Dnmt2 methylates DNA in the structural context of a tRNA. RNA Biology 14 (9) , 1241—1251. 10.1080/15476286.2016.1236170

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Abstract

The amino acid sequence of Dnmt2 is very similar to the catalytic domains of bacterial and eukaryotic DNA-(cytosine 5)-methyltransferases, but it efficiently catalyzes tRNA methylation, while its DNA methyltransferase activity is the subject of controversial reports with rates varying between zero and very weak. By using composite nucleic acid molecules as substrates, we surprisingly found that DNA fragments, when presented as covalent DNA-RNA hybrids in the structural context of a tRNA, can be more efficiently methylated than the corresponding natural tRNA substrate. Furthermore, by stepwise development of tRNAAsp, we showed that this natural Dnmt2 substrate could be engineered to employ RNAs that act like guide RNAs in vitro. The 5’-half of tRNAAsp was able to efficiently guide methylation toward a single stranded tRNA fragment as would result from tRNA cleavage by tRNA specific nucleases. In a more artificial setting, a composite system of guide RNAs could ultimately be engineered to enable the enzyme to perform cytidine methylation on single stranded DNA in vitro.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Landes Bioscience
ISSN: 1547-6286
Date of First Compliant Deposit: 5 February 2019
Date of Acceptance: 7 September 2016
Last Modified: 05 Feb 2019 14:04
URI: http://orca.cf.ac.uk/id/eprint/118988

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