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Blood, 19 February 2009, Vol. 113, No. 8, pp. 1794-1804. Prepublished online as a Blood First Edition Paper on October 10, 2008; DOI 10.1182/blood-2008-05-155812. This Article Full Text (PDF) Supplemental Tables and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-05-155812v1 113/8/1794    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pase, L. Articles by Lieschke, G. J. Search for Related Content PubMed PubMed Citation Articles by Pase, L. Articles by Lieschke, G. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 7, 2008 Accepted September 16, 2008 miR-451 regulates zebrafish erythroid maturation in vivo via its target gata2 Luke Pase, Judith E. Layton, Wigard P. Kloosterman, Duncan Carradice, Peter M. Waterhouse, and Graham J. Lieschke* Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia Ludwig Institute for Medical Research, The Royal Melbourne Hospital, Parkville, Victoria, Australia Hubrecht Laboratory, Centre for Biomedical Genetics, Utrecht, Netherlands Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia CSIRO Plant Industry, Canberra, Australian Capital Territory, Australia * Corresponding author; email: lieschke{at}wehi.edu.au. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Armisen, M. J. Gilchrist, A. Wilczynska, N. Standart, and E. A. Miska Abundant and dynamically expressed miRNAs, piRNAs, and other small RNAs in the vertebrate Xenopus tropicalis Genome Res., October 1, 2009; 19(10): 1766 - 1775. [Abstract] [Full Text] [PDF] O. W. Stockhammer, A. Zakrzewska, Z. Hegedus, H. P. Spaink, and A. H. Meijer Transcriptome Profiling and Functional Analyses of the Zebrafish Embryonic Innate Immune Response to Salmonella Infection J. Immunol., May 1, 2009; 182(9): 5641 - 5653. [Abstract] [Full Text] [PDF]

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