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

Kretov, Dmitry, Isha, Walawalkar, Mora-Martin, Alexandra, Shafik, Andrew, Moxon, Simon and Cifuentes, Daniel (2020) Ago2-dependent processing allows miR-451 to evade the global microRNA turnover elicited during erythropoiesis. Molecular Cell, 78 (2). 317-328.e6. ISSN 1097-2765

[img] PDF (Accepted_Manuscript) - Submitted Version
Restricted to Repository staff only until 18 March 2021.

Download (14MB) | Request a copy


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.

Item Type: Article
Uncontrolled Keywords: ago2,ago2-dependent,dicer,dicer-independent,erythropoiesis,mir-144,mir-451,microrna,non-canonical microrna,zebrafish,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1312
Faculty \ School: Faculty of Science > School of Biological Sciences
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 22 Apr 2020 08:37
Last Modified: 09 Jul 2020 00:01
DOI: 10.1016/j.molcel.2020.02.020

Actions (login required)

View Item View Item