Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells
Competing Repressive Factors Control Bone Morphogenetic Protein 2 (BMP2) in Mesenchymal Cells
复制标题
竞争性抑制因子控制间充质细胞中的骨形态发生蛋白2（BMP 2）
DOI：
10.1002/jcb.25290
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发表时间：
2016-02-01
影响因子：
4
通讯作者：
Rogers, Melissa B.
中科院分区：
文献类型：
--
作者：
Fotinos, Anastasios;Fritz, David T.;Rogers, Melissa B.
骨形态发生蛋白2（BMP 2）合成的数量，时间和位置影响胚胎和成人多能间充质细胞的分化。BMP 2 3 '非翻译区（3' UTR）包含嵌入在通常抑制间充质细胞中的基因表达的序列中的高度保守的富含AU的元件（ARE）。计算分析表明，该位点也可以结合几种microRNA（miRNAs）。虽然miRNAs经常靶向富含AU的区域，但这种ARE是不寻常的，因为miRNAs直接跨越ARE。我们开始描述可能通过这个复杂位点调节Bmp 2表达的因素。活化蛋白HuR（Hu抗原R，ELAVL 1，HGNC：3312）直接结合该ARE并可活化基因表达。证明了miRNA逆转HuR介导的激活。突变和RNA干扰证据也支持AUF 1（AU-因子-1，HNRNPD，HGNC：5036）对间充质细胞中观察到的3 'UTR抑制活性的贡献。有限数量的研究描述了miRNA如何与结合邻近位点的ARE结合蛋白相互作用。这项研究是第一个描述蛋白质/miRNA在同一位点相互作用的研究。(C)2015 Wiley Periodicals，Inc.
The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3'untranslated region (3'UTR) contains a highly conserved AU-rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU-rich regions, this ARE is unusual because the miRNAs directly span the ARE. We began to characterize the factors that may regulate Bmp2 expression via this complex site. The activating protein HuR (Hu antigen R, ELAVL1, HGNC:3312) directly binds this ARE and can activate gene expression. An miRNA was demonstrated to reverse HuR-mediated activation. Mutational and RNA-interference evidence also supports an AUF1 (AU-factor-1, HNRNPD, HGNC: 5036) contribution to the observed repressive activity of the 3'UTR in mesenchymal cells. A limited number of studies describe how miRNAs interact with ARE-binding proteins that bind adjacent sites. This study is among the first to describe protein/miRNA interactions at the same site. (C) 2015 Wiley Periodicals, Inc.