Biogenesis of tRNA-derived small RNAs (tsRNAs). Intron (yellow), 5’-reader (green), and 3’-trailer sequences (brown) are cleaved from pre-tRNAs to generate mature tRNAs. Angiogenin (ANG) in mammals and Ribonuclease-T2 like 1 (Rny1) in yeast cleave nucleotides in the anticodon loops (red) of tRNAs to generate 30-40 nucleotide-long tRNA-derived stress-induced RNAs (tiRNAs), also known as tRNA halves. Despite controversy, DICER, ANG, and RNase T1 were shown to cleave nucleotides in the pseudouridine (T) - or dihydrouridine (D) -loops (blue) of tRNAs to generate 5’- and 3’-tRNA-derived RNA fragments (tRFs), 14-30 nucleotides in length. Internal-tRFs (i-tRFs) are generated by multiple cleavages of tRNAs, and contain internal regions of tRNAs, which are 15-36 nucleotides in length.
