Autophagy selectively regulates miRNA homeostasis.

MicroRNAs (miRNAs) form a class of ~21 nucleotide (nt) RNAs that post-transcriptionally repress partially complementary messenger RNAs. miRNA-mediated silencing is critical for control of many key biological processes such as tumorigenesis, neuronal synaptic plasticity and defense against bacteria and viruses. Thus, unsurprisingly, miRNA biogenesis, abundance and action are under refined feedback control that is only beginning to be experimentally uncovered. We recently discovered that DICER1 and EIF2C/AGO are targeted for degradation by autophagy as miRNA-free entities by the selective autophagy receptor CALCOCO2/NDP52 (calcium binding and coiled-coil domain 2/nuclear dot protein, 52 kDa). Strikingly, autophagy establishes a checkpoint for continued loading of miRNA, and this checkpoint is required for maintenance of miRNA abundance and proper miRNA activity. This newfound role for autophagy in miRNA biology suggests that human diseases exhibiting misregulated autophagy may be interdependent with defects in miRNA-mediated regulation of gene networks.