ALTERNATIVE SPLICING AND GENOMIC STRUCTURE OF THE WILMS-TUMOR GENE-WT1
ALTERNATIVE SPLICING AND GENOMIC STRUCTURE OF THE WILMS-TUMOR GENE-WT1
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DOI：
10.1073/pnas.88.21.9618
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
HOUSMAN, DE
中科院分区：
文献类型：
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作者：
HABER, DA;SOHN, RL;HOUSMAN, DE
染色体11p13 Wilms肿瘤易感基因WT1在调节肾母细胞和性腺组织的增殖和分化中起重要作用。WT1基因由10个外显子组成，编码一种复杂的信使核糖核酸模式：表达四种不同的转录本，存在或不存在两种可供选择的剪接。Splice I由一个单独的外显子组成，编码17个氨基酸，插入在富含Pro的氨基末端和锌指结构域之间。Splice II由5‘端选择性剪接连接产生，导致3个氨基酸插入锌指3和4之间。RNase保护分析表明，在人类和小鼠中，最常见的剪接变体是包含两个备选剪接的剪接变体，而最不常见的是缺失这两个剪接的转录本。剪接变异体的相对分布在正常胎儿肾组织和WT1转录本完整的肾母细胞瘤之间高度保守。在小鼠肾脏和表达WT1的各种小鼠组织中，这些不同的WT1 mRNA物种的比例也作为发育的函数保持不变。这四个WT1mRNA物种在结构和相对水平上的保守性表明，每个编码的多肽对正常的基因功能都有重要的贡献。WT1基因产物对细胞增殖和分化的调控可能涉及四种不同靶点和功能的多肽之间的相互作用。
The chromosome 11p13 Wilms tumor susceptibility gene WT1 appears to play a crucial role in regulating the proliferation and differentiation of nephroblasts and gonadal tissue. The WT1 gene consists of 10 exons, encoding a complex pattern of mRNA species: four distinct transcripts are expressed, the presence or absence of two alternative splices. Splice I consists of a separate exon, encoding 17 amino acids, which is inserted between the proline-rich amino terminus and the zinc finger domains. Splice II arises from the use of an alternative 5' splice junction and results in the insertion of 3 amino acids between zinc fingers 3 and 4. RNase protection analysis demonstrates that the most prevalent splice variant in both human and mouse is that which contains both alternative splices, whereas the least common is the transcript missing both splices. The relative distribution of splice variants is highly conserved between normal fetal kidney tissue and Wilms tumors that have intact WT1 transcripts. The ratio of these different WT1 mRNA species is also maintained as a function of development in the mouse kidney and in various mouse tissues expressing WT1. The conservation in structure and relative levels of each of the four WT1 mRNA species suggests that each encoded polypeptide makes a significant contribution to normal gene function. The control Of cellular proliferation and differentiation exerted by the WT1 gene products may involve interactions between four polypeptides with distinct targets and functions.