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

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

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

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.

http://www.ncbi.nlm.nih.gov/pubmed/20679397