 Abstract micro-ionase, MIRNA, load onto AGO proteins to target M-ionase for translational repression or degradation. However, MIRNA degradation can be triggered when extensively base-paired with target ionase, which induces conformational change of AGO and recruitment of ZSWIM-8 ubiquitin ligase to mark AGO for proteasimal degradation. This target INA-directed MIRNA degradation, TDMD, mechanism appears to be evolutionally conserved, but recent studies have focused on mammalian systems. Indrosophila S2 cells, CISPR, Cas9 knockout of the AGO1 trigger induces MIR-999 degradation, while simultaneous knockdown of MIR-999 leads to increased resistance to hydrogen peroxide-induced stress. These findings suggest that TDMD may play a role in regulating MIRNA levels under certain conditions. This article was offered by Pekasheng, Lu Li, Chen Chi Li, and others.