PUBLICATION
miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2
- Authors
- Pase, L., Layton, J.E., Kloosterman, W.P., Carradice, D., Waterhouse, P.M., and Lieschke, G.J.
- ID
- ZDB-PUB-081022-20
- Date
- 2009
- Source
- Blood 113(8): 1794-1804 (Journal)
- Registered Authors
- Carradice, Duncan, Kloosterman, Wigard, Layton, Judy E., Lieschke, Graham J., Pase, Luke
- Keywords
- none
- MeSH Terms
-
- Age Factors
- Animals
- Cell Differentiation/physiology
- Erythrocytes/cytology*
- Erythroid Cells/cytology*
- Erythropoiesis/genetics*
- GATA2 Transcription Factor/genetics*
- Gene Expression Regulation, Developmental
- MicroRNAs/genetics*
- Mutagenesis
- Phenotype
- RNA, Messenger/metabolism
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 18849488 Full text @ Blood
Citation
Pase, L., Layton, J.E., Kloosterman, W.P., Carradice, D., Waterhouse, P.M., and Lieschke, G.J. (2009) miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2. Blood. 113(8):1794-1804.
Abstract
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 zebrafish 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 erythrocyte maturation. Mnr provided a selectively miR-144/451-deficient background facilitating studies to discern miRNA function and validate candidate targets. Amongst computer-predicted miR-451 targets potentially mediating these biological 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 gata2 down-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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping