title: Defective erythroid differentiation in miR-451 mutant mice mediated by 14-3-3zeta.
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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Patrick
authors.forename: Cheng C
authors.initials: CC
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Tao
authors.forename: Huiyu
authors.initials: H
authors.lastname: Yao
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qi
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schwartz
authors.forename: Lily
authors.initials: L
authors.lastname: Jun-Shen Huang
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D041905:Erythroid Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006400:Hematocrit; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D009841:Oligonucleotides / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D048948:14-3-3 Proteins; D035683:MicroRNAs; C550758:Mirn451 microRNA, mouse; D009841:Oligonucleotides