tRFs, 14-32 nt long RNAs derived from mature or precursor tRNAs, are present in diverse organisms at read counts comparable to miRNAs. TA meta-analysis of short RNA sequence datasets helped us create a comprehensive, relational database of tRFs: tRFdb (http://genome.bioch.virginia.edu/trfdb/). tRFs are precisely generated fragments not produced by the miRNA biogenesis pathway. tRFs are present in all human cell lines, mice, flies, worms, yeasts and even some bacteria and originate from the 5' end (tRF-5a, b, c) and 3' end (tRF-3a, b) of mature tRNAs or from 3' trailer sequences of primary tRNA transcripts (tRF-1). Human PAR-CLIP data shows that tRF-5s and tRF-3s associate with Ago1, 3, and 4 rather than Ago2. The location of the U to C mutation caused by the cross-linking of the tRF to the Ago protein, and the match to the target mRNAs in the PAR-CLIP data demonstrate that a 5' seed sequence of 7-8 bases of the tRF-5 and -3 recognizes the target mRNA in much the same way as microRNAs. Human CLASH data ide...