tRNA renovatio: Rebirth through fragmentation

tRNA function is based on unique structures that enable mRNA decoding using anticodon trinucleotides. These structures interact with specific aminoacyl-tRNA synthetases and ribosomes using 3D shape and sequence signatures. Beyond translation, tRNAs are increasingly recognized as versatile signaling molecules, and they interplay with other RNAs and cellular proteins. These roles arose through a long process of evolution. tRNA fragmentation in particular is not merely random degradation but rather an act of re-creation, generating specific shorter molecules, called tRNA-derived small RNAs (tsRNAs), which exploit their linear sequences and newly arranged 3D structures for unexpected biological functions. Emerging methods to uncover full tRNA/tsRNA sequences and modifications, combined with techniques to study RNA structures and to integrate AI-powered predictions, will enable comprehensive investigations of tRNA fragmentation products and new interaction potentials in relation to their biological functions. We anticipate that these directions will herald a new era for understanding biological complexity and advancing pharmaceutical engineering.