A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells
A neoplastic gene fusion mimics trans-splicing of RNAs in normal human cells
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DOI：
10.1126/science.1156725
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发表时间：
2008-09-05
期刊：
影响因子：
56.9
通讯作者：
Sklar, Jeffrey
中科院分区：
文献类型：
--
作者：
Li, Hui;Wang, Jinglan;Sklar, Jeffrey
产生基因融合的染色体重排是人类肿瘤的常见特征。流行的观点是，所得嵌合转录物和蛋白质是异常的肿瘤特异性产物，其为肿瘤细胞提供生长和/或存活优势。我们发现，正常子宫内膜间质细胞含有一种特异性嵌合RNA，该RNA将染色体7 p15上JAZF 1基因的5'外显子与染色体17 q11上Polycomb组基因JJAZ 1/SUZ 12的3'外显子连接起来，并且该RNA被翻译成JAZF 1-JJAZ 1，一种具有抗凋亡活性的蛋白。JAZF 1-JJAZ 1 RNA似乎是由JAZF 1和JJAZ 1的前体信使RNA之间的生理调节的反式剪接产生的。嵌合RNA和蛋白质与人子宫内膜间质肿瘤中发现的基因融合产生的RNA和蛋白质相同。这些观察结果表明，某些基因融合可能是促肿瘤的，这是由于在发育组织中通常通过RNA的反式剪接产生的嵌合基因产物的组成型表达。
Chromosomal rearrangements that create gene fusions are common features of human tumors. The prevailing view is that the resultant chimeric transcripts and proteins are abnormal, tumor- specific products that provide tumor cells with a growth and/ or survival advantage. We show that normal endometrial stromal cells contain a specific chimeric RNA joining 5' exons of the JAZF1 gene on chromosome 7p15 to 3' exons of the Polycomb group gene JJAZ1/SUZ12 on chromosome 17q11 and that this RNA is translated into JAZF1-JJAZ1, a protein with anti- apoptotic activity. The JAZF1-JJAZ1 RNA appears to arise from physiologically regulated trans- splicing between precursor messenger RNAs for JAZF1 and JJAZ1. The chimeric RNA and protein are identical to those produced from a gene fusion found in human endometrial stromal tumors. These observations suggest that certain gene fusions may be pro- neoplastic owing to constitutive expression of chimeric gene products normally generated by trans- splicing of RNAs in developing tissues.