Submitted May 31, 2007
Accepted September 24, 2007
MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4
Qiang Wang, Zheng Huang, Huiling Xue, Chengcheng Jin, Xiu-Li Ju, Jing-Dong J Han, and Ye-Guang Chen*
State Key Laboratory of Biomembrane & Membrane Biotechnology, Dept of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China
Center for Molecular Systems Biology, Institute of Genetics and Developmental Biology, the Chinese Academy of Sciences, Beijing, China
Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, China
* Corresponding author; email: ygchen{at}tsinghua.edu.cn.
MicroRNAs have been suggested to modulate a variety of cellular events. Here we report that miR-24 regulates erythroid differentiation by influencing the expression of human activin type I receptor ALK4 (hALK4). Ectopic expression of miR-24 reduces the mRNA and protein levels of hALK4 by targeting the 3'-untranslated region of hALK4 mRNA and interferes with activin-induced Smad2 phosphorylation and reporter expression. Furthermore, miR-24 represses the activin-mediated accumulation of hemoglobin, an erythroid differentiation marker, in erythroleukemic K562 cells and decreases erythroid colony-forming and burst-forming units of CD34+ hematopoietic progenitor cells. ALK4 expression is inversely correlated with miR-24 expression during the early stages of erythroid differentiation, and the forced expression of miR-24 leads to a delay of activin-induced maturation of hematopoietic progenitor cells in liquid culture. Thus, our findings define a regulation mode of miR-24 on erythropoiesis by impeding ALK4 expression.
