Aspartyl β-hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin
Aspartyl β-hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin
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DOI：
10.1074/jbc.m006753200
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发表时间：
2000-12-15
影响因子：
4.8
通讯作者：
Friedman, PA
中科院分区：
文献类型：
--
作者：
Dinchuk, JE;Henderson, NL;Friedman, PA
小鼠天冬氨酸β-羟基酶基因(ASPH，BAH)已被克隆和鉴定，其基因组DNA全长200kb，包含24个外显子。在三个主要的BAH相关转录本中，最大的两个(6,629和4,419个碱基对)编码全长蛋白质，唯一不同的是使用了不同的多聚腺苷信号。最小的BAH相关转录本(2,789个碱基对)使用替代的3‘末端外显子，导致蛋白质缺乏催化结构域。BAH的这种非催化亚型在小鼠、人和果蝇中得到了进化上的保守性，建立了克隆抗体试剂，进行了表位映射，并用于确定Northern blotts上的RNA条带与Western blotts上的蛋白质种类之间的关联。小鼠连接素基因是一种钙调素结合蛋白，它在心脏组织BAH/Humbug中表达时，最好使用连接素的第一个外显子，通常是第四个外显子，同时保留阅读框架。因此，三个独立的基因共享共同的外显子和开放的阅读框架，并使用单独的启动子来实现不同组织中的差异表达、剪接和功能，这种不寻常的外显子共享形式表明连接素、BAH和欺骗性蛋白的功能可能是连锁的。
The mouse aspartyl beta -hydroxylase gene (Asph, BAH) has been cloned and characterized, The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila, Monoclonal antibody reagents were generated, epitope-mapped, and used to definitively correlate RNA bands on Northern blots with protein species on Western blots, The gene for mouse junctin, a calsequestrin-binding protein, was cloned and characterized and shown to be encoded from the same locus, When expressed in heart tissue, BAH/humbug; preferably use the first exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading frames and use separate promoters to achieve differential expression, splicing, and function in a variety of tissues, This unusual form of exon sharing suggests that the functions of junctin, BAH, and humbug may be linked.