Ago2-dependent processing allows miR-451 to evade the global microRNA turnover elicited during erythropoiesis

MicroRNAs are sequentially processed by two RNAse III enzymes, Drosha and Dicer. miR-451 is the only known miRNA whose processing bypasses Dicer and instead relies on the slicer activity of Argonaute 2 (Ago2). MiR-451 is highly conserved in vertebrates and regulates erythrocyte maturation, where it becomes the most abundant miRNA. However, the basis for the non-canonical biogenesis of miR-451 is unclear. In this study we tested the hypothesis that miR-144 represses Dicer in a negative feedback loop during erythropoiesis and enhances miR-451 biogenesis. Loss of miR-144 mediated Dicer repression in zebrafish embryos and human cells leads to increased canonical miRNA production and impaired miR-451 maturation.