Target recognition, RNA methylation activity and transcriptional regulation of the Dictyostelium discoideum Dnmt2-homologue (DnmA)

Müller, Sara, Windhof, Indra M, Maximov, Vladimir, Jurkowski, Tomasz ORCID: https://orcid.org/0000-0002-2012-0240, Jeltsch, Albert, Förstner, Konrad U, Sharma, Cynthia M, Gräf, Ralph and Nellen, Wolfgang 2013. Target recognition, RNA methylation activity and transcriptional regulation of the Dictyostelium discoideum Dnmt2-homologue (DnmA). Nucleic Acids Research 41 (18) , 8615—8627. 10.1093/nar/gkt634

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Abstract

Although the DNA methyltransferase 2 family is highly conserved during evolution and recent reports suggested a dual specificity with stronger activity on transfer RNA (tRNA) than DNA substrates, the biological function is still obscure. We show that the Dictyostelium discoideum Dnmt2-homologue DnmA is an active tRNA methyltransferase that modifies C38 in tRNAAsp(GUC)in vitro and in vivo. By an ultraviolet-crosslinking and immunoprecipitation approach, we identified further DnmA targets. This revealed specific tRNA fragments bound by the enzyme and identified tRNAGlu(CUC/UUC) and tRNAGly(GCC) as new but weaker substrates for both human Dnmt2 and DnmA in vitro but apparently not in vivo. Dnmt2 enzymes form transient covalent complexes with their substrates. The dynamics of complex formation and complex resolution reflect methylation efficiency in vitro. Quantitative PCR analyses revealed alterations in dnmA expression during development, cell cycle and in response to temperature stress. However, dnmA expression only partially correlated with tRNA methylation in vivo. Strikingly, dnmA expression in the laboratory strain AX2 was significantly lower than in the NC4 parent strain. As expression levels and binding of DnmA to a target in vivo are apparently not necessarily accompanied by methylation, we propose an additional biological function of DnmA apart from methylation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Oxford University Press (OUP)
ISSN:	0305-1048
Date of Acceptance:	26 June 2013
Last Modified:	25 Oct 2022 13:08
URI:	https://orca.cardiff.ac.uk/id/eprint/118991

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