title: Deletion of Dicer in late erythroid cells results in impaired stress erythropoiesis in mice.
abstract: MicroRNAs (miRNAs) have been shown to influence erythroid lineage commitment and differentiation; however, our knowledge of miRNA function in terminal erythropoiesis remains limited. To address this issue, we generated a novel animal model, where the miRNA-processing enzyme, Dicer, is selectively inactivated in erythropoietin receptor positive erythroid cells beginning with CFU-e/proerythroblast cells. This results in significant depletion of all miRNAs from the proerythroblast stage onwards, with one exception, miR-451, which is processed by Ago2 in a Dicer-independent manner. We observed that mature Dicer-dependent miRNAs, like miR-451, are dispensable under steady-state conditions, but these mutants have an impaired response to stress erythropoiesis, as demonstrated by a delay in recovery from anemia. This defect was specific to later maturing erythroid cells, as progenitor numbers were unaffected. In addition to generating a novel mouse model to study miRNA function in late erythroid cells, we conclude that miRNAs (both Dicer-dependent and independent) act primarily to regulate the optimal response to stress among late erythroid cells.
authors: Division of Hematology, University of Washington, Seattle, WA, USA.
authors: John C H
authors: JC
authors: Byon
authors: Division of Hematology, University of Washington, Seattle, WA, USA.
authors: Steven M
authors: SM
authors: Padilla
authors: Division of Hematology, University of Washington, Seattle, WA, USA. Electronic address: thalp@uw.edu.
authors: Thalia
authors: T
authors: Papayannopoulou
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D060565:Argonaute Proteins / Q000502:physiology; D003114:Colony-Forming Units Assay; D053487:DEAD-box RNA Helicases / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004920:Erythropoiesis / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000633:toxicity; D005813:Genes, Synthetic; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D010659:Phenylhydrazines / Q000633:toxicity; D011401:Promoter Regions, Genetic / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D043244:Ribonuclease III / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D035683:MicroRNAs; C550758:Mirn451 microRNA, mouse; D010659:Phenylhydrazines; D017467:Receptors, Erythropoietin; C030299:phenylhydrazine; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D005472:Fluorouracil