A GATA-1-regulated microRNA locus essential for erythropoiesis
A GATA-1-regulated microRNA locus essential for erythropoiesis
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DOI：
10.1073/pnas.0712312105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Weiss, Mitchell J.
中科院分区：
文献类型：
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作者：
Dore, Louis C.;Amigo, Julio D.;Weiss, Mitchell J.
MicroRNAs （miRNAs）控制着组织发育，但其调控机制尚不清楚。我们使用基因互补策略结合微阵列筛选来鉴定参与红细胞形成的mirna。两个保守的mirna miR 144和miR 451成为关键造血转录因子GATA-1的直接靶点。在体内，GATA-1结合远端上游调控元件，激活RNA聚合酶ii介导的单个共同前体RNA （pri-miRNA）编码两种成熟mirna的转录。利用反义morpholinos耗尽miR 451的斑马鱼胚胎形成红细胞前体，但它们向成熟循环红细胞的发育受到强烈和特异性的损害。这些结果揭示了红细胞生成所需的miRNA位点，并揭示了GATA-1通过其控制这一过程的新调控轴。
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.