Model illustrating the role for Dnmt2 in the codon fidelityIn Dnmt2 wild-type cells, C38 tRNA methylation (red circle) promotes the fidelity of tRNA(Glu) and tRNA(Asp) codons, thus resulting in the translation of correctly folded proteins. In Dnmt2−/− cells, the lack of C38 tRNA methylation (gray circle) reduces the capacity of tRNAs to properly discriminate between Asp and Glu codons, leading to decreased translational fidelity, the production of unfolded proteins, and an aberrant phenotype. 