|ZFIN ID: ZDB-PUB-080309-23|
A GATA-1-regulated microRNA locus essential for erythropoiesis
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., and Weiss, M.J.
|Source:||Proceedings of the National Academy of Sciences of the United States of America 105(9): 3333-3338 (Journal)|
|Registered Authors:||Amigo, Julio, Paw, Barry|
|Keywords:||erythrocyte, hematopoiesis, transcription factor, anemia, gene expression|
|PubMed:||18303114 Full text @ Proc. Natl. Acad. Sci. USA|
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., and 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.
ABSTRACTMicroRNAs (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.