miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2

Pase, L., Layton, J. E., Kloosterman, W. P., Carradice, D., Waterhouse, P. M., & Lieschke, G. J. (2009) miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood, 113(8), pp. 1794-1804.

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We demonstrate that in zebrafish, the microRNA miR-451 plays a crucial role in promoting erythroid maturation, in part via its target transcript gata2. Zebrafish miR-144 and miR-451 are processed from a single precursor transcript selectively expressed in erythrocytes. In contrast to other hematopoietic mutants, the ze-brafish mutant meunier (mnr) showed intact erythroid specification but diminished miR-144/451 expression. Although erythropoiesis initiated normally in mnr, erythrocyte maturation was morphologically retarded. Morpholino knockdown of miR-451 increased erythrocyte immaturity in wild-type embryos, and miR-451 RNA duplexes partially rescued erythroid maturation in mnr, demonstrating a requirement and role for miR-451 in erythro-cyte maturation. mnr provided a selectively miR-144/451-deficient background, facilitating studies to discern miRNA function and validate candidate targets. Among computer-predicted miR-451 targets potentially mediating these biologic effects, the pro-stem cell transcription factor gata2 was an attractive candidate. In vivo reporter assays validated the predicted miR-451/gata2-3'UTR interaction, gata2 down-regulation was delayed in miR-451-knockdown and mnr embryos, and gata2 knockdown partially restored erythroid maturation in mnr, collectively confirming gata2down-regulation as pivotal for miR-451-driven erythroid maturation. These studies define a new genetic pathway promoting erythroid maturation (mnr/miR-451/gata2) and provide a rare example of partial rescue of a mutant phenotype solely by miRNA overexpression. © 2009 by The American Society of Hematology.

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ID Code: 65815
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
Additional URLs:
Keywords: microRNA, transcription factor GATA 2, animal cell, article, cell maturation, cell mutant, controlled study, down regulation, embryo, erythroid cell, erythropoiesis, gene expression, gene function, gene locus, gene overexpression, hematopoietic cell, nonhuman, phenotype, priority journal, protein interaction, protein targeting, RNA processing, zebra fish, Age Factors, Animals, Cell Differentiation, Erythrocytes, Erythroid Cells, GATA2 Transcription Factor, Gene Expression Regulation, Developmental, MicroRNAs, Mutagenesis, RNA, Messenger, Zebrafish, Zebrafish Proteins, PMCID: PMC2647672
DOI: 10.1182/blood-2008-05-155812
ISSN: 0006-4971
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400)
Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > PLANT BIOLOGY (060700)
Divisions: Current > Schools > School of Earth, Environmental & Biological Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Copyright Owner: American Society of Hematology
Deposited On: 08 Jan 2014 03:14
Last Modified: 27 Jan 2015 06:45

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