PUBLICATION
Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis
- Authors
- Kretov, D.A., Walawalkar, I.A., Mora-Martin, A., Shafik, A.M., Moxon, S., Cifuentes, D.
- ID
- ZDB-PUB-200403-127
- Date
- 2020
- Source
- Molecular Cell 78(2): 317-328.e6 (Journal)
- Registered Authors
- Cifuentes, Daniel, Moxon, Simon
- Keywords
- Ago2, Ago2-dependent, Dicer, Dicer-independent, erythropoiesis, miR-144, miR-451, microRNA, non-canonical microRNA, zebrafish
- MeSH Terms
-
- Animals
- Argonaute Proteins/genetics*
- DEAD-box RNA Helicases/genetics
- Erythropoiesis/genetics*
- Gene Expression Regulation, Developmental/genetics
- Humans
- MicroRNAs/genetics*
- RNA Interference
- Ribonuclease III/genetics
- Zebrafish/genetics
- Zebrafish/growth & development
- PubMed
- 32191872 Full text @ Mol. Cell
Citation
Kretov, D.A., Walawalkar, I.A., Mora-Martin, A., Shafik, A.M., Moxon, S., Cifuentes, D. (2020) Ago2-Dependent Processing Allows miR-451 to Evade the Global MicroRNA Turnover Elicited during Erythropoiesis. Molecular Cell. 78(2):317-328.e6.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping