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缺陷的RNA处理和可逆细胞衰老中的ELOA介导的转录延长表明通过转录衰老
Saeid Parast1, Simai Wang2, Marta Iwanaszko1
1Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
像负延长因子 (NELF) 和SPT6这样的转录延长因子调节RNA处理和细胞衰老. 埃隆金A (ELOA) 与NELF相互作用,控制基因转录终止和细胞衰老.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 转录延长因子 (例如,PAF1,NELF,SPT4/5,SPT6) 在人类细胞系中具有不同的作用.
- 了解RNA处理和细胞功能的这些因素的精确机制至关重要.
研究的目的:
- 整合长读和短读RNA-seq数据以量化单分子分辨率的转录异形使用量.
- 为了识别延长因子特定的RNA处理调节子及其对细胞衰老的影响.
- 调查埃隆金A (ELOA) 在转录调节中的作用及其与衰老的联系.
主要方法:
- 在人类细胞系中利用了辅酶诱导降解系统.
- 综合长短读取RNA测序 (RNA-seq) 数据,用于高分辨率的转录分析.
- 进行了基因抑制器屏幕和基因淘汰实验.
- 评估RNA聚合酶II (RNAPII) 进程性和与衰老相关的基因表达.
主要成果:
- 鉴定了特定于延长因子的RNA处理调节子,包括受NELF和SPT6.6影响的增老调节子.
- 由于NELF或SPT6的枯竭,导致可逆的生长停止和老化相关基因的上调.
- ELOA被认为是NELF枯竭效应的抑制剂,调节RNAPII在转录终点 (TESs) 以后的进展.
- 急性ELOA耗尽损害了基因3'末端的RNAPII进程性,ELOA损失促进了老化纤维细胞的生长.
结论:
- 已建立的依赖NELF/ELOA的机制,控制转录延长和RNA处理.
- 将这些机制与细胞衰老和衰老过程联系起来.
- 突出了延长因子在调节基因表达和细胞命运中的功能相互作用.
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