Our speaker for this week's biology seminar is Gozde Korkmaz.
MicroRNA-376b controls autophagy by targeting Atg4C and Beclin 1
Autophagy is a cellular catabolic mechanism conserved from yeast to mammals. Recycling and degradation of long-lived proteins and organelles by autophagy maintain cellular homeostasis. Furthermore, activation of autophagy can lead to cell death or survival depending on stress conditions. Hence, it is essential to understand molecular pathways regulating autophagy. In this study, we demonstrated the role of a microRNA, hsa-miR-376b (miR-376b), in the regulation of autophagic activity. miR-376b expression blocked starvation- and rapamycin-induced autophagy and led to a decrease in the cellular levels of two key autophagy mRNA and proteins, namely Atg4C and Beclin 1. miR-376b-specific antagomirs (anti-miRNAs) suppressing endogenous miRNA effect resulted in an increase in cellular Atg4C and Beclin 1 levels. Moreover, autophagic activity was recovered in rescue experiments where miR-376b and target genes were co-expressed. Using luciferase assays, we showed that potential miRNA binding regions in the 3’UTR regions of target genes were functional and their mutations blocked miR-376b effect. We also demonstrated that endogenous miR-376b levels were upregulated in response to various stress and death-inducing stimuli. Therefore, we introduce miR-376b as a novel regulator of autophagy and Atg4C and Beclin 1 as its cellular effectors. Implications of miRNA regulation of autophagy during cell death and survival will be discussed.