Autophagy modulates miRNA-mediated gene silencing and selectively degrades AIN-1/GW182 in C. elegans.

MicroRNAs (miRNAs) post-transcriptionally repress gene expression via the miRNA-induced silencing complex (miRISC), which includes miRNA, Argonaute and a GW182 family member. Here we show that in Caenorhabditis elegans, miRNA-mediated gene silencing is modulated by macroautophagy, a lysosome-mediated degradation process. Loss of autophagy activity suppresses developmental defects caused by partially impaired silencing of miRNA targets including the let-7 family and lsy-6. The C. elegans GW182 homolog AIN-1 is itself selectively degraded by autophagy and colocalizes with the p62 homolog SQST-1 in autophagy mutants. Thus, autophagy activity modulates miRNA-mediated gene silencing and degrades a core miRISC component.