A GATA-1-regulated microRNA locus essential for erythropoiesis

Louis C. Dore, Julio D. Amigo, Camila O. Dos Santos, Zhe Zhang, Xiaowu Gai, John W. Tobias, Duonan Yu, Alyssa M. Klein, Christine Dorman, Weisheng Wu, Ross C. Hardison, Barry H. Paw, Mitchell J. Weiss

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244 Scopus citations

Abstract

MicroRNAs (miRNAs) control tissue development, but their mechanism of regulation is not well understood. We used a gene complementation strategy combined with microarray screening to identify miRNAs involved in the formation of erythroid (red blood) cells. Two conserved miRNAs, miR 144 and miR 451, emerged as direct targets of the critical hematopoietic transcription factor GATA-1. In vivo, GATA-1 binds a distal upstream regulatory element to activate RNA polymerase II-mediated transcription of a single common precursor RNA (pri-miRNA) encoding both mature miRNAs. Zebrafish embryos depleted of miR 451 by using antisense morpholinos form erythroid precursors, but their development into mature circulating red blood cells is strongly and specifically impaired. These results reveal a miRNA locus that is required for erythropoiesis and uncover a new regulatory axis through which GATA-1 controls this process.

Original languageEnglish (US)
Pages (from-to)3333-3338
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number9
DOIs
StatePublished - Mar 4 2008

All Science Journal Classification (ASJC) codes

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    Dore, L. C., Amigo, J. D., Dos Santos, C. O., Zhang, Z., Gai, X., Tobias, J. W., Yu, D., Klein, A. M., Dorman, C., Wu, W., Hardison, R. C., Paw, B. H., & Weiss, M. J. (2008). A GATA-1-regulated microRNA locus essential for erythropoiesis. Proceedings of the National Academy of Sciences of the United States of America, 105(9), 3333-3338. https://doi.org/10.1073/pnas.0712312105