Figure 6.

A proposed model of the regulation of stress-induced tiRNA production. Under normal conditions, ANG (and other RNase A superfamily enzymes) is inhibited by RNH1. Once cells are exposed to stress, the RNases become activated through RNH1 dissociation, cleaving tRNAs into tiRNAs. A part of tiRNAs is repaired to intact tRNAs before separation. Under the condition where oxidative stress coexists, the repair of tRNAs is repressed due to inhibition of the RTCB ligase complex, resulting in increased levels of separated tiRNAs that contribute to cell protection against adverse conditions. We propose that the net amount of tiRNA production is estimated by two factors, a trigger (RNH1 dissociation) and a booster (RTCB inhibition).