剪接因子PTBP1与RUNX1相互作用,对于白血病细胞存活是必需的
bioRxiv : the preprint server for biology
|June 6, 2025
概括
聚胺管结合蛋白1 (PTBP1) 与白血病细胞中的Runt相关转录因子1 (RUNX1) 相互作用. 这种相互作用对代谢基因表达至关重要,影响白血病细胞存活.
科学领域:
- 血液形成和白血病研究研究
- 分子生物学分子生物学
- 癌症基因组学 癌症基因组学
背景情况:
- 与Runt相关的转录因子1 (RUNX1) 对血液形成至关重要,在白血病中经常发生突变.
- 基因组脱酶酶1 (HDAC1) 与RUNX1合作,在活性转录中发挥作用.
- 建议HDAC1在调节RUNX1复合元件方面具有非歇斯顿功能.
研究的目的:
- 在白血病中识别新的RUNX1相互作用伙伴.
- 研究这些合作伙伴在基因调节和RNA剪接中的作用.
- 阐明白血病中RUNX1-PTBP1相互作用的功能意义.
主要方法:
- 使用了蛋白质组学,基因组学和长读转录组学.
- 染色素分析被用来绘制因子占用率的地图.
- 功能性研究包括评估PTBP1损失对AML细胞的影响.
主要成果:
- 聚胺管结合蛋白1 (PTBP1) 被确定为一个RUNX1交互因子,依赖HDAC1.1.
- RUNX1和PTBP1广泛共占基因促进体,特别是在活跃转录的基因中.
- 失去PTBP1导致广泛的RNA剪接变化和代谢基因的表达减少.
结论:
- PTBP1以HDAC1依赖的方式与RUNX1结合,并与目标基因促进体同定位.
- 白血病细胞中的PTBP1损失会损害代谢基因表达,导致生长减少,糖解和细胞死亡.
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