tRNA derived small RNAs—Small players with big roles

In the past 2 decades, small non-coding RNAs derived from tRNA (tsRNAs or tRNA derived fragments; tRFs) have emerged as new powerful players in the field of small RNA mediated regulation of gene expression, translation, and epigenetic control. tRFs have been identified from evolutionarily divergent organisms from Archaea, the higher plants, to humans. Recent studies have confirmed their roles in cancers and other metabolic disorders in humans and experimental models. They have been implicated in biotic and abiotic stress responses in plants as well. In this review, we summarize the current knowledge on tRFs including types of tRFs, their biogenesis, and mechanisms of action. The review also highlights recent studies involving differential expression profiling of tRFs and elucidation of specific functions of individual tRFs from various species. We also discuss potential considerations while designing experiments involving tRFs identification and characterization and list the available bioinformatics tools for this purpose.