Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3zeta

Genes Dev. 2010 Aug 1;24(15):1614-9. doi: 10.1101/gad.1942810.

Abstract

Erythrocyte formation occurs throughout life in response to cytokine signaling. We show that microRNA-451 (miR-451) regulates erythropoiesis in vivo. Mice lacking miR-451 display a reduction in hematrocrit, an erythroid differentiation defect, and ineffective erythropoiesis in response to oxidative stress. 14-3-3zeta, an intracellular regulator of cytokine signaling that is repressed by miR-451, is up-regulated in miR-451(-/-) erythroblasts, and inhibition of 14-3-3zeta rescues their differentiation defect. These findings reveal an essential role of 14-3-3zeta as a mediator of the proerythroid differentiation actions of miR-451, and highlight the therapeutic potential of miR-451 inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • Animals
  • Cell Differentiation*
  • Erythroid Cells / cytology*
  • Erythroid Cells / metabolism
  • Erythroid Cells / pathology
  • Erythropoiesis / genetics*
  • Gene Expression Regulation, Developmental / drug effects
  • Hematocrit
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Mutation
  • Oligonucleotides / pharmacology
  • Up-Regulation

Substances

  • 14-3-3 Proteins
  • MicroRNAs
  • Mirn451 microRNA, mouse
  • Oligonucleotides