Xrp1控制着应激反应程序对结合体组功能障碍的控制
Dimitrije Stanković1, Luke S Tain1, Mirka Uhlirova1
1Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne 50931, Germany.
Nucleic acids research
|February 2, 2024
概括
在U5小核核核糖核蛋白颗粒 (snRNP) 的缺乏导致R-循环和细胞循环停止. Xrp1-Irbp18异构体调解了这种应激反应,突出了拼接拼接.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 结合酶体对共转录的mRNA前处理对基因表达和基因组稳定性至关重要.
- U5小核核核糖核蛋白颗粒 (snRNP) 是结合体的重要组成部分.
研究的目的:
- 为了研究 U5 snRNP 缺乏在 Drosophila 形象细胞中的后果.
- 为了确定链接spliceosome故障与细胞应激反应的分子机制.
主要方法:
- 产生U5 snRNP缺乏的多索菲拉形象细胞.
- 转录组分析 (RNA-seq).
- R-循环检测和量化. 在R-循环检测和量化.
- 对于压力标志物的西部涂抹 (JNK,p53).
- 通过RNA干扰 (RNAi) 来淘汰Xrp1和Irbp18.
主要成果:
- U5 snRNP 缺乏导致广泛的转录组变化和突变性 R-循环积累.
- 细胞表现出应激反应,细胞循环停止,增加蛋白质翻译,细胞大小和细胞亡.
- Xrp1-Irbp18异构体被确定为压力程序的关键调解者.
- Knockdown 的 Xrp1 或 Irbp18 减少了压力信号,恢复了细胞循环,并抑制了细胞亡,但没有修复拼接缺陷.
结论:
- U5 snRNP 功能障碍触发了涉及R环和Xrp1-Irbp18异构体的DNA损伤反应通路.
- 精确的拼接对于维持细胞和组织平衡至关重要.
- 在Xrp1-Irbp18异构体作为一个传感器用于spliceosome缺陷,并调解压力诱导的细胞衰老.
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