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.
Patrick
David M
DM
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Zhang
Cheng C
CC
Tao
Ye
Y
Yao
Huiyu
H
Qi
Xiaoxia
X
Schwartz
Robert J
RJ
Jun-Shen Huang
Lily
L
Olson
Eric N
EN
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
D048948:14-3-3 Proteins; D035683:MicroRNAs; C550758:Mirn451 microRNA, mouse; D009841:Oligonucleotides