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Kretov, Dmitry, Isha, Walawalkar, Mora-Martin, Alexandra, Shafik, Andrew, Moxon, Simon 
ORCID: https://orcid.org/0000-0003-4644-1816 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
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Abstract
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: | 22 Oct 2022 05:49 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/74786 |
| DOI: | 10.1016/j.molcel.2020.02.020 |
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