miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2
Data(s) |
2009
|
---|---|
Resumo |
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. |
Identificador | |
Publicador |
American Society of Hematology |
Relação |
DOI:10.1182/blood-2008-05-155812 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. |
Direitos |
American Society of Hematology |
Fonte |
School of Earth, Environmental & Biological Sciences; Science & Engineering Faculty |
Palavras-Chave | #060000 BIOLOGICAL SCIENCES #060400 GENETICS #060700 PLANT BIOLOGY #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 |
Tipo |
Journal Article |