Tac1 regulation by RNA-binding protein and miRNA in bone marrow stroma:: Implication for hematopoietic activity
Tac1 regulation by RNA-binding protein and miRNA in bone marrow stroma:: Implication for hematopoietic activity
复制标题
DOI：
10.1016/j.bbi.2007.10.009
复制
发表时间：
2008-05-01
影响因子：
15.1
通讯作者：
Rameshwar, Pranela
中科院分区：
文献类型：
--
作者：
Murthy, Raghav G.;Greco, Steven J.;Rameshwar, Pranela
造血是由有限数量的相对较少的造血干细胞（hsc）产生免疫细胞和血细胞的过程。在成人中，造血发生在成人骨髓（BM）中，在基质细胞的支持下。这种支持在一定程度上是通过造血调节因子的产生来实现的，这些调节因子属于细胞因子和神经肽/神经递质家族，它们通过特定受体调节它们的作用。因此，基质细胞可能是神经-造血-免疫轴的中枢。这项研究的重点是Tac1，它编码造血调节因子，属于神经肽的快激肽家族。我们检测了Tac1在骨髓基质中的转录后调控。由于该基因在基质中可诱导，我们选择了具有不同造血作用的细胞因子：刺激干细胞因子（SCF）、广效IL-11和抑制性tgf - β 1。在37℃下，IL-11和scf刺激的基质中，Tac1 mRNA和细胞质提取物在15分钟后出现RNA移位，而tgf - β 1刺激的基质提取物在室温下5分钟后出现RNA移位。通过检测与Tac1 mRNA的3'非翻译区相互作用的mirna，观察到另一个水平的转录后调控。综上所述，本研究表明细胞因子诱导的miRNA下调和rna结合蛋白(s)参与了BM基质中Tac1的转录后调控。作为造血刺激剂或抑制剂的细胞因子的广泛类别可能。取决于Tac1 mRNA的rna结合蛋白(s)的亲和力，以及降解或稳定特定mirna的能力。(c) 2007爱思唯尔公司版权所有。
Hematopoiesis is the process by which immune and blood cells are produced from a finite number of relatively few hematopoietic stem cells (HSCs). In adults, hematopoiesis occurs in the adult bone marrow (BM), with the support of stromal cells. This support partly occurs through the production of hematopoietic, regulators belonging to the families of cytokines and neuropeptides/neurotransmitters, which mediate their actions through specific receptors. Thus, stromal cells could be central to the neural-hematopoietic-immune axis. This study focuses on Tac1, which encodes hematopoietic regulators belonging to the tachykinin family of neuropeptides. We examined post-transcriptional regulation of Tac1 in BM stroma. Since this gene is inducible in stroma, we selected cytokines with varying hematopoietic effects: stimulator Stem Cell Factor (SCF), broad-acting IL-11 and suppressive TGF-beta 1. RNA shift with Tac1 mRNA and cytoplasmic extracts from IL-11 and SCF-stimulated stroma showed RNA shift after 15 min at 37 degrees C, whereas a shift was detected with extracts from TGF-beta 1-stimulated stroma after 5 min at room temperature. Another level of post-transcriptional regulation was observed by the detection of miRNAs that interact with the 3' untranslated region of Tac1 mRNA. In summary, this study showed that cytokine induced miRNA downregulation and RNA-binding protein(s) are involved in post-transcriptional regulation of Tac1 in BM stroma. The broad categories of cytokines as hematopoietic stimulators or inhibitors might. depend on the avidity of RNA-binding protein(s) for Tac1 mRNA, as well as the ability to degrade or stabilize the specific miRNAs. (c) 2007 Elsevier Inc. All rights reserved.