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

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.

Pubmed ID: 20679397

Authors

  • Patrick DM
  • Zhang CC
  • Tao Y
  • Yao H
  • Qi X
  • Schwartz RJ
  • Jun-Shen Huang L
  • Olson EN

Journal

Genes & development

Publication Data

August 1, 2010

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL089966
  • Agency: NHLBI NIH HHS, Id: HL09530601A1
  • Agency: NHLBI NIH HHS, Id: R01 HL053351
  • Agency: NHLBI NIH HHS, Id: R01 HL053351-05
  • Agency: NHLBI NIH HHS, Id: R01 HL077439
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-02
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-03
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-04
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-05
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-06
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-06W1
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-07
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-08
  • Agency: NHLBI NIH HHS, Id: R01 HL093039
  • Agency: NHLBI NIH HHS, Id: R01 HL093039-01A1
  • Agency: NHLBI NIH HHS, Id: R01 HL093039-01A1W1
  • Agency: NHLBI NIH HHS, Id: R01 HL093039-02
  • Agency: NHLBI NIH HHS, Id: R01 HL093039-03
  • Agency: NHLBI NIH HHS, Id: R37 HL053351
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-08S1
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-09
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-09S1
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-10
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-11
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-12
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-13
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-14
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-15

Mesh Terms

  • 14-3-3 Proteins
  • Animals
  • Cell Differentiation
  • Erythroid Cells
  • Erythropoiesis
  • Gene Expression Regulation, Developmental
  • Hematocrit
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs
  • Mutation
  • Oligonucleotides
  • Up-Regulation