It has been discovered in 2006 that the Dnmt2 enzyme unexpectedly is a tRNA methyltransferase that modifies the C38 position of tRNA-Asp, but its exact molecular function of this modification remained unclear. In our paper we document that the C38 methylation is important for the tRNA-Asp recognition of the aspartyl-tRNA synthetase, which transfers Asparate on the tRNA and by this prepares it for protein biosynthesis. Lack of Dnmt2 causes reduced translational efficiency of Asp-rich proteins. Our data show that Dnmt2 mediated tRNA-Asp methylation could represent a novel mechanism of translational fine tuning of groups of proteins containing poly-Asp sequences that for example has a role in stress response. Homopolymeric stretches of particular amino acids other than poly-Asp are widespread in the human proteome, but their function often is not clear. Based on our findings, they may affect protein biosynthesis using a similar mechanism triggered by a modification of the corresponding tRNA.