The miR-144/451 locus is required for erythroid homeostasis.
The process of erythropoiesis must be efficient and robust to supply the organism with red bloods cells both under condition of homeostasis and stress. The microRNA (miRNA) pathway was recently shown to regulate erythroid development. Here, we show that expression of the locus encoding miR-144 and miR-451 is strictly dependent on Argonaute 2 and is required for erythroid homeostasis. Mice deficient for the miR-144/451 cluster display a cell autonomous impairment of late erythroblast maturation, resulting in erythroid hyperplasia, splenomegaly, and a mild anemia. Analysis of gene expression profiles from wild-type and miR-144/451-deficient erythroblasts revealed that the miR-144/451 cluster acts as a "tuner" of gene expression, influencing the expression of many genes. MiR-451 imparts a greater impact on target gene expression than miR-144. Accordingly, mice deficient in miR-451 alone exhibited a phenotype indistinguishable from miR-144/451-deficient mice. Thus, the miR-144/451 cluster tunes gene expression to impart a robustness to erythropoiesis that is critical under conditions of stress.
Rasmussen
Kasper D
KD
European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo Scalo, 00015, Italy.
Simmini
Salvatore
S
Abreu-Goodger
Cei
C
Bartonicek
Nenad
N
Di Giacomo
Monica
M
Bilbao-Cortes
Daniel
D
Horos
Rastislav
R
Von Lindern
Marieke
M
Enright
Anton J
AJ
O'Carroll
Dónal
D
D000740:Anemia / Q000235:genetics / Q000473:pathology; D000818:Animals; D060565:Argonaute Proteins; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D004900:Erythroblasts / Q000378:metabolism / Q000473:pathology; D041905:Erythroid Cells / Q000378:metabolism* / Q000473:pathology; D004920:Erythropoiesis / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics*; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism
C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D015852:Eukaryotic Initiation Factor-2; C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; C550758:Mirn451 microRNA, mouse