ALTERNATIVE SPLICING OF HUMAN DYSTROPHIN MESSENGER-RNA GENERATES ISOFORMS AT THE CARBOXY TERMINUS
ALTERNATIVE SPLICING OF HUMAN DYSTROPHIN MESSENGER-RNA GENERATES ISOFORMS AT THE CARBOXY TERMINUS
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DOI：
10.1038/338509a0
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发表时间：
1989-04-06
期刊：
影响因子：
64.8
通讯作者：
KUNKEL, LM
中科院分区：
文献类型：
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作者：
FEENER, CA;KOENIG, M;KUNKEL, LM
肌营养不良蛋白是Duchenne/Becker肌营养不良基因座的蛋白质产物。它的相对分子质量为427，000，由一个大的RNA转录物编码，该转录物由分布在人类X染色体1 -5的200万个碱基对上的65个以上外显子加工而成。我们已经使用聚合酶链反应6来观察这些外显子中的任何一个是否在表达肌营养不良蛋白的不同组织中交替使用。如大鼠肌营养不良蛋白7所报道的，我们发现人肌营养不良蛋白转录物的第一外显子在脑和肌肉中是不同的，这表明肌营养不良蛋白的表达可以通过使用不同的启动子在这些组织中进行差异调节。抗肌萎缩蛋白转录物的3′端可以选择性剪接，以产生许多在羧基1结构域不同的同种型;这是抗肌萎缩蛋白中唯一与相关细胞骨架α-辅肌动蛋白没有任何相似性的结构域3。这些替代转录物产生肌营养不良蛋白分子，其可与表达肌营养不良蛋白的组织的不同蛋白质相互作用。
DYSTROPHIN is the protein product of the Duchenne/Becker muscular dystrophy locus. It has a relative molecular mass of 427,000 and is encoded by a large RNA transcript processed from more than 65 exons spread over two million base pairs of the human X chromosome1–5. We have used the polymerase chain reaction6to see whether any of these exons are used alternatively in the different tissues that express dystrophin. As reported for rat dystrophin7, we find that the first exon of the human dystrophin transcript is different in brain and muscle, indicating that dystrophin expression could be differentially regulated in these tissues by usage of distinct promoters. The 3′ end of the dystrophin transcript can be alternatively spliced to create numerous isoforms differing at their carboxy 1 domains; this is the only domain of dystrophin that does not share any similarity with the related cytoskeletal α-actinins3. These alternative transcripts yield dystrophin molecules which may interact with different proteins of the tissues expressing dystrophin.