Role of tRNA modifications in human diseases

•Recent findings suggest a role for tRNA modifications in complex human diseases.•Implications for cancer, diabetes, neurological diseases, and mitochondrial-linked diseases.•Novel therapeutic approaches based on tRNA modifications can be devised.•There is a need to further our knowledge on the dynamics of hypomodified tRNAs.

Transfer RNAs (tRNAs) are key for efficient and accurate protein translation. To be fully active, tRNAs need to be heavily modified post-transcriptionally. Growing evidence indicates that tRNA modifications and the enzymes catalyzing such modifications may play important roles in complex human pathologies. Here, we have compiled current knowledge that directly link tRNA modifications to human diseases such as cancer, type 2 diabetes (T2D), neurological disorders, and mitochondrial-linked disorders. The molecular mechanisms behind these connections remain, for the most part, unknown. As we progress towards the understanding of the roles played by hypomodified tRNAs in human disease, novel areas of therapeutic intervention may be discovered.