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
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping