The cell and stress‐specific canonical and noncanonical tRNA cleavage

Following stress, transfer RNA (tRNA) is cleaved to generate tRNA halves (tiRNAs). These tiRNAs have been shown to repress protein translation. Angiogenin was considered the main enzyme that cleaves tRNA at its anticodon to generate 35–45 nucleotide long tiRNA halves, however, the recent reports indicate the presence of angiogenin‐independent cleavage. We previously observed tRNA cleavage pattern occurring away from the anticodon site. To explore this noncanonical cleavage, we analyze tRNA cleavage patterns in rat model of ischemia–reperfusion and in two rat cell lines. In vivo mitochondrial tRNAs were prone to this noncanonical cleavage pattern. In vitro, however, cytosolic and mitochondrial tRNAs could be cleaved noncanonically. Our results show an important regulatory role of mitochondrial stress in angiogenin‐mediated tRNA cleavage. Neither angiogenin nor RNH1 appear to regulate the noncanonical tRNA cleavage. Finally, we verified our previous findings of the role of Alkbh1 in regulating tRNA cleavage and its impact on noncanonical tRNA cleavage. During oxidative stress, transfer RNA (tRNA) is cleaved at the anticodon via angiogenin to generate 35–45 nt long tiRNAs. This process regulates protein translation. Rashad et al. show a noncanonical form of tRNA cleavage, occurring away from the anticodon and is angiogenin in dependent. This noncanonical cleavage is in‐part regulated by tRNA methylation (via Alkbh1). Moreover, they show an important role of mitochondrial stress in regulating canonical and noncanonical tRNA cleavage.