DIFFERENTIAL EXPRESSION AND LIGAND REGULATION OF THE RETINOIC ACID RECEPTOR-ALPHA AND RECEPTOR-BETA GENES
DIFFERENTIAL EXPRESSION AND LIGAND REGULATION OF THE RETINOIC ACID RECEPTOR-ALPHA AND RECEPTOR-BETA GENES
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DOI：
10.1002/j.1460-2075.1989.tb03394.x
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发表时间：
1989-02-01
期刊：
影响因子：
11.4
通讯作者：
DEJEAN, A
中科院分区：
文献类型：
--
作者：
DETHE, H;MARCHIO, A;DEJEAN, A
维甲酸(RA)是一种维生素A衍生物，在细胞分化和胚胎模式形成等生物学过程中发挥重要作用。最近已经鉴定了两种人类维甲酸受体(RARα和β)。这些受体由两个基因编码，它们与RA的亲和力不同，提示这两个核受体在介导RA不同的生物学效应中可能具有不同的作用。在这里，我们证明了RARα和β在它们的mRNAs表达调节上的不同。在被分析的不同人体组织中发现了不同水平的RARα和β转录本。此外，用维甲酸处理人肝癌细胞后，RARβ的mRNA水平迅速增加10到50倍，而RARα的mRNA表达不受影响。RARβ转录的诱导不需要从头合成蛋白质，但可被RNA合成的抑制剂完全取消。核转录延长分析表明，RARβmRNA的诱导机制存在于转录水平。这些数据表明，RARβ基因是RA的主要靶点。RAR基因表达调控的差异可能是维甲酸生理学的一个基本方面，并可能被证明在分析RA的形态发生特性方面特别重要。
Retinoic acid (RA) is a vitamin A derivative that exhibits major effects on biological processes such as cell differentiation and embryo pattern formation. Two human retinoic acid receptors (RAR alpha and beta) have been recently characterized. These receptors are encoded by two genes and their affinities for RA differ, suggesting that these two nuclear receptors may have distinct roles in mediating the varied biological effects of RA. Here we show that RAR alpha and beta differ in the regulation of expression of their mRNAs. Different levels of RAR alpha and beta transcripts were found in the various human tissues analysed. In addition, treatment of human hepatoma cells with RA leads to a rapid 10‐ to 50‐fold increase in RAR beta mRNA levels, whereas RAR alpha mRNA expression is not affected. The induction of RAR beta transcription does not require de novo protein synthesis but is completely abolished by inhibitors of RNA synthesis. Nuclear transcript elongation assays indicate that the mechanism of RAR beta mRNA induction lies at the transcriptional level. These data demonstrate that the RAR beta gene is a primary target for RA. The differences in regulation of RAR gene expression might be a fundamental aspect of retinoid physiology and may prove especially important in the analysis of the morphogenic properties of RA.