Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences

Shanmugam, Raghuvaran, Fierer, Jacob, Kaiser, Steffen, Helm, Mark, Jurkowski, Tomasz P ORCID: https://orcid.org/0000-0002-2012-0240 and Jeltsch, Albert 2015. Cytosine methylation of tRNA-Asp by DNMT2 has a role in translation of proteins containing poly-Asp sequences. Cell discovery 1 , 15010. 10.1038/celldisc.2015.10

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Abstract

The Dnmt2 RNA methyltransferase catalyses the methylation of C38 in the anticodon loop of tRNA-Asp, but the molecular role of this methylation is unknown. Here, we report that mouse aspartyl-tRNA synthetase shows a four to fivefold preference for C38-methylated tRNA-Asp. Consistently, a 30% reduced charging level of tRNA-Asp was observed in Dnmt2 knockout (KO) murine embryonic fibroblast cells. Gene expression analysis with fluorescent reporter proteins fused to an N-terminal poly-Asp sequence showed that protein synthesis of poly-Asp-tagged reporter proteins was reduced in Dnmt2 KO cells as well. The same effect was observed with endogenous proteins containing poly-Asp sequences, indicating that Dnmt2-mediated C38 methylation of tRNA-Asp regulates the translation of proteins containing poly-Asp sequences. Gene ontology searches for proteins containing poly-Asp sequences in the human proteome showed that a significant number of these proteins have roles in transcriptional regulation and gene expression. Hence, the Dnmt2-mediated methylation of tRNA-Asp exhibits a post-transcriptional regulatory role by controlling the synthesis of a group of target proteins containing poly-Asp sequences.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
ISSN:	2056-5968
Date of Acceptance:	26 March 2015
Last Modified:	25 Oct 2022 13:09
URI:	https://orca.cardiff.ac.uk/id/eprint/119004

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