TRANSFORMED HUMAN-CELLS PRODUCE A NEW FIBRONECTIN ISOFORM BY PREFERENTIAL ALTERNATIVE SPLICING OF A PREVIOUSLY UNOBSERVED EXON
TRANSFORMED HUMAN-CELLS PRODUCE A NEW FIBRONECTIN ISOFORM BY PREFERENTIAL ALTERNATIVE SPLICING OF A PREVIOUSLY UNOBSERVED EXON
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DOI：
10.1002/j.1460-2075.1987.tb02509.x
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发表时间：
1987-08-01
期刊：
影响因子：
11.4
通讯作者：
BARALLE, FE
中科院分区：
文献类型：
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作者：
ZARDI, L;CARNEMOLLA, B;BARALLE, FE
纯化和氨基酸序列分析的纤连蛋白（FN）的蛋白水解片段从转化的人细胞表明，这些FN分子的高百分比含有额外的氨基酸序列，这是目前只有在一个非常低的百分比的FN分子从正常的成纤维细胞和血浆FN是检测不到的。这种新的氨基酸序列在FN分子中引入了一个对许多蛋白水解酶非常敏感的位点。通过分析细胞的mRNA和geonmic克隆，我们已经证明，该序列来自FN mRNA前体的差异剪接模式，这导致转化细胞中的额外III型同源重复序列（ED-B）的高水平表达，该序列由以前未观察到的外显子编码。在这里，我们还报告了这个新外显子的完整序列。这些结果表明，在恶性细胞中，调节FN mRNA前体剪接的机制被改变。
Purification and amino acid sequence analysis of a proteolytic fragment of fibronectin (FN) from transformed human cells demonstrated that a high percentage of these FN molecules contains an extra amino acid sequence which is present only in a very low percentage of FN molecules from normal fibroblasts and is undetectable in plamsa FN. This new amino acid sequence introduces into the FN molecule a site very sensitive to a number of proteolytic enzymes. By analyzing the cellular mRNA and geonmic clones, we have demonstrated that this sequence derives from a differential splicing pattern of the FN mRNA precursors, which leads in transformed cells to a high-level expression of an extra type III homology repeat (ED-B) coded for by a previously unobserved exon. Here we also report the complete sequence of this new exon. These results demonstrate that in malignant cells the mechanisms regulating the splicing of FN mRNA precursors are altered.