一种瘤基因融合模仿了正常人体细胞中RNA的转链拼接
Hui Li1, Jinglan Wang, Gil Mor
1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
概括
正常的子宫内膜细胞通过RNA转接产生JAZF1-JJAZ1融合蛋白,它具有抗亡活性. 这一发现表明,一些基因融合可能通过构成性地表达通常短暂的化学产品来促进癌症.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 基因融合在人类瘤中很常见,通常被视为异常,瘤特异性产物驱动癌症生长.
- 主流假设表明,嵌合体转录和蛋白质赋予瘤细胞增长或生存优势.
研究的目的:
- 研究JAZF1-JJAZ1仿制RNA和蛋白质的起源和功能.
- 为了确定正常发生的转接事件是否可以解释瘤中发现的基因融合.
主要方法:
- 在正常子宫内膜细胞中分析RNA转录.
- 识别仿真RNA分子的标识.
- 蛋白质表达分析和功能测定对抗亡活性.
- 将瘤衍生的基因融合与自然发生的化学产物进行比较.
主要成果:
- 正常的子宫内膜层细胞表达一种由JAZF1和JJAZ1前体信使RNA转接形成的嵌合RNA (JAZF1-JJAZ1).
- 这种嵌合式RNA被转化为JAZF1-JJAZ1蛋白,表现出抗亡活性.
- 自然存在的JAZF1-JJAZ1RNA和蛋白质与子宫内膜层瘤中基因融合产生的相同.
结论:
- 生理学调节的转接可以产生具有功能意义的嵌合基因产物,例如抗亡活性.
- 正如在瘤中看到的那样,这些通常是短暂的化学产品的构成表达可能是一个亲新形成的机制.
- 这挑战了所有与瘤相关的基因融合仅仅是异常,异常事件的观点.
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