MicroRNA-495 regulates starvation-induced autophagy by targeting ATG3

The functions of some essential autophagy genes are regulated by microRNAs. However, an ATG3-modulating microRNA has never been reported. Here we show that the transcription of miR-495 negatively correlates with the translation of ATG3 under nutrient-deprived or rapamycin-treated conditions. miR-495 targets ATG3 and regulates its protein levels under starvation conditions. miR-495 also inhibits starvation-induced autophagy by decreasing the number of autophagosomes and by preventing LC3-I-to-LC3-II transition and P62 degradation. These processes are reversed by the overexpression of an endogenous miR-495 inhibitor. Re-expression of Atg3 without miR-495 response elements restores miR-495-inhibited autophagy. miR-495 sustains cell viability under starvation conditions but has no effect under hypoxia. Moreover, miR-495 inhibits etoposide-induced cell death. In conclusion, miR-495 is involved in starvation-induced autophagy by regulating Atg3.