MULTIPLE ISOFORMS OF THE MOUSE RETINOIC ACID RECEPTOR ALPHA ARE GENERATED BY ALTERNATIVE SPLICING AND DIFFERENTIAL INDUCTION BY RETINOIC ACID
MULTIPLE ISOFORMS OF THE MOUSE RETINOIC ACID RECEPTOR ALPHA ARE GENERATED BY ALTERNATIVE SPLICING AND DIFFERENTIAL INDUCTION BY RETINOIC ACID
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DOI：
10.1002/j.1460-2075.1991.tb07921.x
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发表时间：
1991-01-01
期刊：
影响因子：
11.4
通讯作者：
CHAMBON, P
中科院分区：
文献类型：
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作者：
LEROY, P;KRUST, A;CHAMBON, P
连同先前描述的小鼠视黄酸受体α-1（mRAR-alpha-1，以前称为mRAR-alpha-0），我们在此分离并表征了总共七种mRAR-alpha cDNA同种型（mRAR-alpha-1至alpha-7）。 这些同种型由单个基因的mRAR-α初级转录物通过至少8个不同外显子与编码其共同B区氨基酸序列的外显子的选择性剪接产生。 所有这些同种型的不同之处在于它们的5 '-非翻译区（5'-UTR），并且在mRAR-α-1和2的情况下，还在于编码N-末端A区的序列，已知N-末端A区对于核受体超家族的其他成员的差异反式激活是重要的。 此外，编码mRAR-α 3和α 4 cDNA亚型的开放阅读框（ORF）的序列在其5'端保持开放，这表明这两种亚型也可能编码具有独特A区氨基酸序列的RAR-α。 发现两种主要亚型mRAR-α-1和2在小鼠成体和胎儿组织以及P19和F9胚胎癌（EC）细胞系中差异表达。 有趣的是，与mRAR-alpha-1亚型的表达相反，mRAR-alpha-2的表达在EC细胞中由视黄酸（RA）诱导，从而表明在mRAR-alpha基因的5'区域中存在两个启动子，其在对RA的响应方面不同。 小鼠和人类RAR-α-1和α-2 cDNA亚型序列之间的保守性，如通过Southern印迹中的交叉杂交或通过DNA序列分析所见，连同它们的表达差异模式，强烈表明它们在胚胎发生期间和在成人中执行特定功能。
Together with the previously described mouse retinoic acid receptor alpha-1 (mRAR-alpha-1, formerly mRAR-alpha-0), we have isolated and characterized here a total of seven mRAR-alpha cDNA isoforms (mRAR-alpha-1 to alpha-7). These isoforms are generated from mRAR-alpha primary transcript(s) of a single gene by alternative splicing of at least eight different exons with the exon which encodes the amino acid sequence of their common B region. All of these isoforms differ in their 5'-untranslated regions (5'-UTRs) and, in the case of mRAR-alpha-1 and alpha-2, also in the sequences encoding the N-terminal A region which is known to be important for differential trans-activation by other members of the nuclear receptor superfamily. In addition, the sequences encoding the open reading frames (ORFs) of mRAR-alpha-3 and alpha-4 cDNA isoforms remain open to their very 5' ends, which suggests that these two isoforms may also encode RAR-alpha-s with unique A region amino acid sequences. The two predominant isoforms, mRAR-alpha-1 and alpha-2, were found to be differentially expressed in mouse adult and fetal tissues, as well as in P19 and F9 embryonal carcinoma (EC) cell lines. Interestingly, the expression of mRAR-alpha-2, in contrast to that of the mRAR-alpha-1 isoform, was induced by retinoic acid (RA) in EC cells, thus suggesting the presence of two promoters in the 5' region of the mRAR-alpha gene, which differ in their response to RA. The conservation between mouse and human RAR-alpha-1 and alpha-2 cDNA isoform sequences, as seen by cross-hybridization in Southern blots or by DNA sequence analysis, together with their differential patterns of expression, strongly suggests that they perform specific functions during embryogenesis and in the adult.