MUTUALLY EXCLUSIVE EXON SPLICING OF THE CARDIAC CALCIUM-CHANNEL ALPHA-1 SUBUNIT GENE GENERATES DEVELOPMENTALLY REGULATED ISOFORMS IN THE RAT-HEART
MUTUALLY EXCLUSIVE EXON SPLICING OF THE CARDIAC CALCIUM-CHANNEL ALPHA-1 SUBUNIT GENE GENERATES DEVELOPMENTALLY REGULATED ISOFORMS IN THE RAT-HEART
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DOI：
10.1073/pnas.89.4.1497
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发表时间：
1992-02-15
影响因子：
11.1
通讯作者：
SCHWARTZ, A
中科院分区：
文献类型：
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作者：
DIEBOLD, RJ;KOCH, WJ;SCHWARTZ, A
从大鼠基因组文库中分离了几个克隆，以进一步鉴定L类电压依赖性钙通道第四基序(IVS3)的第三跨膜区内的可变区。我们在此报道，这种多样性源于含有单个相邻外显子的初级转录本的选择性剪接，每个外显子编码IVS3区域的唯一序列。通过对上游和下游外显子侧翼的基因组图谱和对相关外显子/内含子边界的广泛序列分析，获得了互斥剪接机制的确凿证据。S1核酸酶保护实验表明，IVS3的两种异构体在新生大鼠和胎鼠心脏中表达相同，而在成年大鼠心脏中只有一种亚型表达。结果表明，当兴奋性发生重大变化时，心脏组织中存在一个由选择性剪接外显子介导的重要发育调节开关。
Several clones were isolated from a rat genomic library in order to further characterize a region of variability within the third membrane-spanning region of the fourth motif (IVS3) of the L-type voltage-dependent calcium channel. We report here that this diversity arises from alternative splicing of a primary transcript containing a single pair of adjacent exons each encoding a unique sequence for the IVS3 region. Definitive proof of a mutually exclusive splicing mechanism was obtained by genomic mapping of flanking upstream and downstream exons and by extensive sequence analysis of the relevant exon/intron boundaries. S1 nuclease protection experiments revealed that both variant forms of the IVS3 were equally expressed in newborn and fetal rat heart, whereas only a single isoform predominated in adult rat heart. The results demonstrate the existence of an important developmentally regulated switch mediated by alternatively spliced exons in cardiac tissue at a time when major changes in excitation occur.