Epitranscriptomics: Dnmt2-mediated RNA methylation

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Dnmt2 is a widely conserved enzyme that contains all the catalytic motifs of a canonical DNA methyltransferase. However, the DNA methyltransferase activity of Dnmt2 enzymes is very low and we have shown that Dnmt2 functions as a multisubstrate tRNA methyltransferase (Raddatz et al., 2013). We continue to develop sequencing-based methods for the analysis of transcriptome-wide methylation patterns. Furthermore, the analysis of mouse mutants revealed novel functions of tRNA methylation in tRNA stabilization (Tuorto et al., 2012) and in the regulation of translational fidelity (Tuorto et al., 2015). Our current experiments explore the role of Dnmt2-mediated tRNA methylation in genome recoding. This represents a fundamentally novel concept for understanding cellular adaptation in health and disease.

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