AGO1 associates with microRNAs (miRNAs) and regulates mRNAs through cleavage and translational repression. AGO1 homeostasis entails DCL1-dependent production of miR168 from MIR168a and MIR168b transcripts, post-transcriptional stabilization of miR168 by AGO1, and AGO1-catalyzed miR168-guided cleavage of AGO1 mRNA.