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Mol Cell. 2020 Mar 12. pii: S1097-2765(20)30113-1. doi: 10.1016/j.molcel.2020.02.020. [Epub ahead of print]

Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis.

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Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
School of Biological Sciences, University of East Anglia, Norwich, UK.
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA. Electronic address:


MicroRNAs (miRNAs) 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. Here, we show that Ago2 is less efficient than Dicer in processing pre-miRNAs, but this deficit is overcome when miR-144 represses Dicer in a negative-feedback loop during erythropoiesis. Loss of miR-144-mediated Dicer repression in zebrafish embryos and human cells leads to increased canonical miRNA production and impaired miR-451 maturation. Overexpression of Ago2 rescues some of the defects of miR-451 processing. Thus, the evolution of Ago2-dependent processing allows miR-451 to circumvent the global repression of canonical miRNAs elicited, in part, by the miR-144 targeting of Dicer during erythropoiesis.


Ago2; Ago2-dependent; Dicer; Dicer-independent; erythropoiesis; miR-144; miR-451; microRNA; non-canonical microRNA; zebrafish

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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