Li Hui, Wang Jinglan, Mor Gil, Sklar Jeffrey
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Science. 2008 Sep 5;321(5894):1357-61. doi: 10.1126/science.1156725.
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.
产生基因融合的染色体重排是人类肿瘤的常见特征。普遍观点认为，由此产生的嵌合转录本和蛋白质是异常的肿瘤特异性产物，为肿瘤细胞提供生长和/或生存优势。我们发现，正常子宫内膜基质细胞含有一种特定的嵌合RNA，它将7号染色体p15上JAZF1基因的5'外显子与17号染色体q11上多梳蛋白组基因JJAZ1/SUZ12的3'外显子连接起来，并且这种RNA被翻译成具有抗凋亡活性的JAZF1-JJAZ1蛋白。JAZF1-JJAZ1 RNA似乎源于JAZF1和JJAZ1前体信使RNA之间受生理调节的反式剪接。这种嵌合RNA和蛋白质与在人类子宫内膜基质肿瘤中发现的基因融合所产生的RNA和蛋白质相同。这些观察结果表明，某些基因融合可能由于发育组织中RNA反式剪接正常产生的嵌合基因产物的组成性表达而具有促肿瘤作用。
