Multiple and tissue-specific promoter control of gonadal and non-gonadal prolactin receptor gene expression
Multiple and tissue-specific promoter control of gonadal and non-gonadal prolactin receptor gene expression
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DOI：
10.1074/jbc.271.17.10242
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发表时间：
1996-04-26
影响因子：
4.8
通讯作者：
Dufau, ML
中科院分区：
文献类型：
--
作者：
Hu, ZZ;Zhuang, L;Dufau, ML
催乳素受体(PRLRs)广泛表达，在催乳素靶组织中存在多种编码PRLRs的mRNA转录本。目前，PRLR基因表达调控的分子基础尚不清楚。对PRLRmRNAs在性腺和非性腺组织中表达的5‘非翻译区及其基因组结构进行了分析，发现了三个可供选择的第一外显子，分别命名为EL(1)、EL(2)和EL(3)。这些外显子中的每一个被选择性地剪接到包含翻译起始密码子的第三外显子之前的公共非编码外显子(外显子2，核苷酸-115至-56)。外显子EL(1)、EL(2)和EL(3)的选择性利用以及外显子2的选择性剪接在PRLR转录本中产生多个5‘-非翻译区。这些可供选择的第一外显子(EL(1)、EL(2)和EL(3))被发现在体内以组织特异性的方式利用。EL(1)主要在卵巢中表达，EL(2)在肝脏中特异表达，EL(3)在间质细胞中以主要形式表达，在卵巢和肝脏中以次要形式表达。基因组5‘侧翼区分别含有启动EL(1)、EL(2)和EL(3)转录的三个可能的PRLR基因启动子(PI、PII和PIII)。EL(1)来自-549处的单个位置，EL(2)来自-405、-461和-506处的多个位置，EL(3)来自-340和-351的两个主要位置。这些发现表明，多个启动子控制着PRLR基因的转录，并为不同组织中PRLR表达的差异调控提供了分子基础。
Prolactin receptors (PRLRs) are widely expressed, and multiple mRNA transcripts encoding PRLRs are present in prolactin target tissues. The molecular basis for the control of the PRLR gene expression is currently unknown. Analyses of the 5'-untranslated regions of PRLR mRNAs expressed in gonadal and non-gonadal tissues and their genomic organization revealed three alternative first exons designated as El(1), El(2), and El(3). Each of these exons is alternatively spliced to a common noncoding exon (exon 2, nucleotides -115 to -56) that precedes the third exon containing the translation initiation codon. Alternative utilization of exons El(1), El(2), and El(3), as well as alternative splicing of exon 2, generates multiple 5'-untranslated regions in PRLR transcripts. These alternative first exons (El(1), El(2), and El(3)) were found to be utilized in a tissue-specific manner in vivo. El(1) is predominantly expressed in the ovary, El(2) is specifically expressed in the liver, and El(3) is expressed as a predominant form in the Leydig cell and as a minor form in the ovary and liver. Genomic 5'-flanking regions containing the three putative PRLR gene promoters (PI, PII, and PIII) that initiate the transcription of El(1), El(2), and El(3), respectively, were identified. El(1) was found to initiate from a single site at -549, El(2) from multiple sites at -405, -461, and -506, and El(3) from two major sites at -340 and -351. These findings indicate that multiple promoters control transcription of the PRLR gene and provide a molecular basis for the differential regulation of PRLR expression in diverse tissues.