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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A Regulatory Interplay Between Mir-27a And Runx1 During Megakaryopoiesis
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A Regulatory Interplay Between Mir-27a And Runx1 During Megakaryopoiesis

机译：Megakaryopoiesis期间Mir-27a和Runx1之间的调节相互作用

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摘要

The transcription factor Runx1 is a key regulator of definitive hematopoiesis in the embryo and the adult. Lineage-specific expression of Runx1 involves transcription and post-transcription control through usage of alternative promoters and diverse 3'UTR isoforms, respectively. We identified and mapped microRNA (miR) binding sites on Runx1 3'UTR and show that miR-27a, miR-9, miR-18a, miR-30c, and miR-199a~* bind and post-transcriptionally attenuate expression of Runx1. miR-27a impacts on both the shortest (0.15 kb) and longest (3.8 kb) 3'UTRs and, along with additional miRs, might contribute to translation attenuation of Runx1 mRNA in the myeloid cell line 416B. Whereas levels of Runx1 mRNA in 416B and the B cell line 70Z were similar, the protein levels were not. Large amounts of Runx1 protein were found in 70Z cells, whereas only minute amounts of Runx1 protein were made in 416B cells and overexpression of Runx1 in 416B induced terminal differentiation associated with megakaryocytic markers. Induction of megakaryocytic differentiation in K562 cells by 12-o-tetradeca-noylphorbol-13-acetate markedly increased miR-27a expression, concomitantly with binding of Runx1 to miR-27a regulatory region. The data indicate that miR-27a plays a regulatory role in megakaryocytic differentiation by attenuating Runx1 expression, and that, during megakaryopoiesis, Runx1 and miR-27a are engaged in a feedback loop involving positive regulation of miR-27a expression by Runx1.
机译：转录因子Runx1是胚胎和成体中最终造血功能的关键调节因子。 Runx1的谱系特异性表达涉及分别通过使用替代启动子和多种3'UTR同工型进行转录和转录后控制。我们在Runx1 3'UTR上鉴定并绘制了microRNA（miR）结合位点，并显示miR-27a，miR-9，miR-18a，miR-30c和miR-199a〜*结合并转录后减弱Runx1的表达。 miR-27a对最短（0.15 kb）和最长（3.8 kb）3'UTR都有影响，并且与其他miR一起可能会影响髓样细胞系416B中Runx1 mRNA的翻译减弱。 416B和B细胞系70Z中Runx1 mRNA的水平相似，而蛋白质水平则不同。在70Z细胞中发现大量Runx1蛋白，而在416B细胞中仅产生少量Runx1蛋白，并且416B中Runx1的过表达诱导了与巨核细胞标志物相关的终末分化。 12-邻-十四烷基-noylphorbol-13-乙酸盐诱导的K562细胞巨核细胞分化显着增加了miR-27a表达，并伴有Runx1与miR-27a调控区的结合。数据表明，miR-27a通过减弱Runx1表达在巨核细胞分化中起调节作用，并且在巨核细胞生成过程中，Runx1和miR-27a参与了一个反馈环，涉及Runx1对miR-27a表达的正向调控。

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