MUTUALLY EXCLUSIVE EXON SPLICING OF THE CARDIAC CALCIUM-CHANNEL ALPHA-1 SUBUNIT GENE GENERATES DEVELOPMENTALLY REGULATED ISOFORMS IN THE RAT-HEART

被引:92
作者
DIEBOLD, RJ [1 ]
KOCH, WJ [1 ]
ELLINOR, PT [1 ]
WANG, JJ [1 ]
MUTHUCHAMY, M [1 ]
WIECZOREK, DF [1 ]
SCHWARTZ, A [1 ]
机构
[1] UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45229
关键词
D O I
10.1073/pnas.89.4.1497
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:1497 / 1501
页数:5
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