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

David M. Patrick, Chengcheng Zhang, Ye Tao, Huiyu Yao, Xiaoxia Qi, Robert J. Schwartz, Jun-Shen Huang, Eric N Olson

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1614-1619
Number of pages6
JournalGenes and Development
Volume24
Issue number15
DOIs
StatePublished - Aug 1 2010

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Keywords

  • 14-3-3ζ
  • Antagomir
  • Erythroid differentiation
  • miR-451
  • microRNA-451
  • ywhaz

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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