The human μ opioid receptor gene:: 5′ regulatory and intronic sequences
The human μ opioid receptor gene:: 5′ regulatory and intronic sequences
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DOI：
10.1007/s001090050246
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发表时间：
1998-06-01
影响因子：
4.7
通讯作者：
Hoehe, MR
中科院分区：
文献类型：
--
作者：
Wendel, B;Hoehe, MR
人MU阿片受体(HMOR)与内源性和外源性配体相互作用，介导其特有的效应、奖赏、依赖和镇痛。特别是与吗啡结合，它代表了当代医学中最有价值的止痛药的靶点。对其结构、调控和表达的分析将有助于阐明阿片类药物/吗啡诱导作用的分子过程。因此，我们在hMOR的基因组组织方面做出了重要的贡献，将先前已知的cDNA序列信息(2162bp)扩展到总计6968bp：我们已经确定了5‘调控区的2412bp，确定了翻译起始密码子上游的一个主要和三个次要转录起始点216、285、358和373bp，以及潜在的转录调控因子的结合位点，包括糖皮质激素反应元件、cAMP反应元件、激活蛋白1和阴阳-1盒的可能的顺式作用增强子基序。此外，我们还分析了内含子1和3的5‘和3’核苷酸序列以及内含子2的完整序列。除了参与RNA剪接的经典共识序列外，我们还发现了调控选择性剪接的内含子重复序列((A)/(T)GGG)，这些内含子的突变会导致人类疾病。在hmor基因中也观察到了类似的遗传变异。综上所述，提供的序列信息将允许对该基因进行全面的分析，以寻找与药物滥用的易感性或阿片剂介导的镇痛中的个体差异有关的等位基因变异。
The human mu opioid receptor (hMOR) interacts with endogenous and exogenous ligands to mediate its characteristic effects, reward, dependence, and analgesia. Specifically binding morphine, it represents the target of the most valuable pain killer in contemporary medicine. Analysis of its structure, regulation, and expression will elucidate molecular processes involved in opioid/morphine-induced actions. Thus we have contributed significant information on the genomic organization of hMOR, extending the previously known cDNA sequence information (2162 bp) up to a total of 6968 bp: we have determined 2412 bp of 5' regulatory region, identified one major and three minor transcription initiation sites 216, 285, 358, and 373 bp upstream from the translation start codon, as well as potential binding sites for transcriptional regulatory factors, including putative cis-acting enhancer motifs for a glucocorticoid response element, cAMP response elements, activator proteins 1, and Yin Yang-1 boxes. Moreover, we have analyzed the 5' and 3' nucleotide sequences of introns 1 and 3 and the complete sequence of intron 2. In addition to the classical consensus sequences involved in RNA splicing, we have identified intronic repeats ((A)/(T)GGG) found to regulate alternative splicing, mutations of which cause human disease. A similar genetic variant is observed in the hMOR gene. Taken together, the sequence information presented will allow comprehensive analysis of this gene for allelic variations associated with vulnerability to drug abuse or individual differences in opiate mediated analgesia.