The epitranscriptome in translation regulation: mRNA and tRNA modifications as the two sides of the same coin?

Translation of mRNA is a highly regulated process that is tightly coordinated with cotranslational protein maturation. Recently, mRNA modifications and tRNA modifications - the so called epitranscriptome - have added a new layer of regulation that is still poorly understood. Both types of modifications can affect codon-anticodon interactions, thereby affecting mRNA translation and protein synthesis in similar ways. Here, we describe an updated view on how the different types of modifications can be mapped, how they affect translation, how they trigger phenotypes and discuss how the combined action of mRNA and tRNA modifications coordinate translation in health and disease.