DIFFERENTIALLY EXPRESSED ISOFORMS OF THE MOUSE RETINOIC ACID RECEPTOR-BETA ARE GENERATED BY USAGE OF 2 PROMOTERS AND ALTERNATIVE SPLICING
DIFFERENTIALLY EXPRESSED ISOFORMS OF THE MOUSE RETINOIC ACID RECEPTOR-BETA ARE GENERATED BY USAGE OF 2 PROMOTERS AND ALTERNATIVE SPLICING
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DOI：
10.1002/j.1460-2075.1991.tb07922.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：
--
作者：
ZELENT, A;MENDELSOHN, C;CHAMBON, P
使用锚定PCR，分离出小鼠视黄酸受体β的三种不同cDNA亚型[mRAR-β-1，mRAR-β-2（以前称为mRAR-β-0）和mRAR-β-3]，它们通过差异启动子使用和可变剪接从同一基因产生。 这三种亚型编码具有不同N-末端A区和相同B-F区的RAR蛋白。 编码mRAR-β-3 A区的前59个氨基酸的序列与mRAR-β-1的整个A区相同。 然而，mRAR-β-3区域A的序列与mRAR-β-1的序列的不同之处在于，在编码mRAR-β-1的A和B区域的外显子之间剪接的81个核苷酸长的推定外显子中编码另外27个C末端氨基酸。 mRAR-β-1和β-3 cDNA与mRAR-β-2的5 '-非翻译（5'-UTR）和A区编码序列完全不同。 这种N-末端变异性，在一个区域，这被证明是重要的细胞类型特异性差异靶基因的反式激活其他核受体，表明这三个mRAR-β亚型可能是功能不同的。 从小鼠到人类的RAR-β同种型序列的保守性，如通过Southern印迹或DNA序列分析的交叉杂交所见，以及它们在各种小鼠组织中的差异表达模式，证实了这一观点。 此外，mRNA分析数据表明，mRAR-beta-2，其表达占主导地位的RA处理的胚胎癌（EC）和胚胎干（ES）细胞，可能是重要的，在早期阶段的发展。 另一方面，mRAR-beta-1和beta-3主要在胎儿和成人大脑中表达，可能在中枢神经系统的发育中发挥某些特定作用。
Using anchored PCR, three different cDNA isoforms of the mouse retinoic acid receptor beta [mRAR-beta-1, mRAR-beta-2 (formerly mRAR-beta-0) and mRAR-beta-3], generated from the same gene by differential promoter usage and alternative splicing, were isolated. These three isoforms encode RAR proteins with different N-terminal A regions and identical B-F regions. The sequence encoding the first 59 amino acids of the mRAR-beta-3 A region is identical with the entire A region of mRAR-beta-1. However, the sequence of mRAR-beta-3 region A differs from that of mRAR-beta-1 by an additional 27 C-terminal amino acids encoded in an 81 nucleotide-long putative exon which is spliced in between the exons encoding the A and B regions of mRAR-beta-1. Both mRAR-beta-1 and beta-3 cDNAs differ entirely from mRAR-beta-2 in their 5'-untranslated (5'-UTR) and A region coding sequences. This N-terminal variability, in a region which was shown to be important for cell-type specific differential target gene trans-activation by other nuclear receptors, suggests that the three mRAR-beta isoforms may be functionally distinct. The conservation of RAR-beta isoform sequences from mouse to human, as seen by cross-hybridization on Southern blots or DNA sequence analysis, as well as their differential patterns of expression in various mouse tissues, corroborates this view. Additionally, the mRNA analysis data suggest that mRAR-beta-2, whose expression predominates in RA-treated embryonal carcinoma (EC) and embryonic stem (ES) cells, may be important during early stages of development. mRAR-beta-1 and beta-3, on the other hand, which are predominantly expressed in fetal and adult brain, may play some specific role in the development of the central nervous system.