Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis
Regnase-1-mediated post-transcriptional regulation is essential for hematopoietic stem and progenitor cell homeostasis
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DOI：
10.1038/s41467-019-09028-w
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发表时间：
2019-03-06
影响因子：
16.6
通讯作者：
Takakura, Nobuyuki
中科院分区：
文献类型：
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作者：
Kidoya, Hiroyasu;Muramatsu, Fumitaka;Takakura, Nobuyuki
造血干细胞和祖细胞（HSPCs）的自我更新和分化之间的平衡维持造血稳态，其失败可导致造血障碍。HSPC命运由来自骨髓小生境的信号控制，导致干细胞转录网络的改变。Regnase-1是具有RNA酶活性的CCCH锌指蛋白家族的成员，通过降解靶mRNA介导转录后调节活性。Regnase-1在炎症相关细胞因子表达中的确切功能已被探索，但其在造血中的功能尚未阐明。在这里，我们表明Regnase-1通过调节Gata 2和Tal 1 mRNA的稳定性来调节HSPCs的自我更新。此外，我们发现Regnase-1的功能障碍导致异常造血的快速发作。因此，我们的数据表明，Regnase-1介导的转录后调节是HSPC维持所必需的，并表明它代表了白血病肿瘤抑制因子。
The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor.