The multifaceted regulatory potential of tRNA-derived fragments

tRNAs have been discovered in the late 1950-ies of the last century and have subsequently been characterized biochemically, genetically and structurally as amino-acid delivering molecules for protein biosynthesis. First reports of stable tRNA-derived cleavage products have been reported in the late 1970-ies (1), but at that time they were mostly regarded as functionless degradation products. The advent of high-throughput sequencing techniques in the last years allowed the discovery of an unforeseen variety of small non-protein-coding RNAs (ncRNAs), including tRNA-derived RNA fragments (typically referred to as tdRs or tRFs), in all domains of life. Post-transcriptional RNA cleavage encompasses all sorts of transcripts including mRNAs as well as ncRNAs thus amplifying the biological repertoire of cellular RNomes significantly. Most of these small ncRNAs are involved in different steps of gene regulation. The most studied and well understood small ncRNA regulators are the ~22 nt long miRNA and siRNA involved in postranscriptional gene silencing, a process termed RNA interference (RNAi).