The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis

The discovery of the genetic code and tRNAs as decoders of the code transformed life science. However, after establishing the role of tRNAs in protein synthesis, the field moved to other parts of the RNA world. Now, tRNA research is blooming again, with demonstration of the involvement of tRNAs in various other pathways beyond translation and in adapting translation to environmental cues. These roles are linked to the presence of tRNA sequence variants known as isoacceptors and isodecoders, various tRNA base modifications, the versatility of protein binding partners and tRNA fragmentation events, all of which collectively create an incalculable complexity. This complexity provides a vast repertoire of tRNA species that can serve various functions in cellular homeostasis and in adaptation of cellular functions to changing environments, and it likely arose from the fundamental role of RNAs in early evolution.