MicroRNA miR-24 inhibits erythropoiesis by targeting activin type I receptor ALK4.
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.
Wang
Qiang
Q
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Huang
Zheng
Z
Xue
Huiling
H
Jin
Chengcheng
C
Ju
Xiu-Li
XL
Han
Jing-Dong J
JD
Chen
Ye-Guang
YG
D020413:3' Untranslated Regions / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D028341:Activins / Q000378:metabolism; D018952:Antigens, CD34; D002454:Cell Differentiation / Q000502:physiology*; D004920:Erythropoiesis / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D017930:Genes, Reporter; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D018952:Antigens, CD34; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D028341:Activins; C498932:ACVR1B protein, human; D030201:Activin Receptors, Type I