PT  - JOURNAL ARTICLE
AU  - Sherif Rashad
AU  - Takaaki Abe
AU  - Teiji Tominaga
AU  - Kuniyasu Niizuma
TI  - The cell and stress specific dynamics of <em>in vivo</em> and <em>in vitro</em> canonical and non-canonical tRNA cleavage
AID  - 10.1101/2020.02.04.934695
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.04.934695
4099  - http://biorxiv.org/content/early/2020/02/05/2020.02.04.934695.short
4100  - http://biorxiv.org/content/early/2020/02/05/2020.02.04.934695.full
AB  - Following stress, tRNA is cleaved to generate tRNA halves (tiRNAs). These stress induced small RNAs have been shown to regulate processes such as translation initiation and stem cell function. To date, angiogenin (ANG) is considered the main enzyme that cleaves tRNA at its anti-codon site to generate 35 ~ 45 nucleotide long 5’ and 3’ tiRNA halves. Herein, using rat model of focal ischemia and 2 different rat neuronal cell lines exposed to different stresses, we show that tRNA cleavage is a selective process that is heterogenous amongst different tRNAs. We also report for the first time the existence of non-canonical tRNA cleavage that is angiogenin independent and that tRNA cleavage is cell specific and stress specific. Moreover, we show that angiogenin-mediated tRNA cleavage itself is tRNA selective and that angiogenin overexpression doesn’t lead to the expected overt tRNA cleavage in the cells. Finally, the proposed enzymes responsible for this non-canonical tRNA cleavage do not appear to be regulated by RNH1, the angiogenin inhibitor.