RNA外体驱动的RNA处理指导了展开的蛋白质反应的持续时间
Laura Matabishi-Bibi1, Coralie Goncalves2, Anna Babour1,2
1Université Paris Cité, INSERM U944 and CNRS 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, 75475 Paris Cedex 10, France.
Nucleic acids research
|February 25, 2025
概括
核RNA外基因组控制着展开蛋白质反应 (UPR) 的持续时间. 无活化Rrp6阻断了UPR信号传输,增强了细胞对内细胞网膜应激的抵抗力.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 细胞区块激活适应性程序,在压力期间恢复平衡.
- 长时间激活未折叠蛋白应答 (UPR) 由于缺陷的内 плазма网膜 (ER) 蛋白质稳定可能导致细胞死亡.
- UPR是一种保护的转录反应,对于管理ER压力至关重要.
研究的目的:
- 调查核RNA外体在调节UPR持续时间方面的作用.
- 确定Rrp6失活对UPR信号传递和细胞应激抵抗性的影响.
- 阐明RNA外基因组控制UPR持续时间的分子机制.
主要方法:
- 研究了核RNA外体的功能,一个核糖核酶复合体.
- 利用了Rrp6的基因失活,Rrp6是RNA外体的核催化子单元.
- 分析了RNA物种的处理,包括UPR调节器Hac1.1的信使RNA.
- 评估了UPR信号持续时间和细胞对ER压力的抵抗力.
主要成果:
- 无活化Rrp6限制了UPR信号传输,使其抵抗ER压力.
- 在Rrp6无活化后,观察到未经加工的RNA物种的积累.
- 这种积累会转移RNA处理机器,限制Hac1mRNA的成熟.
- 在ER应力时,Rrp6表达被下调,导致UPR失活.
结论:
- 核RNA外体,通过其Rrp6子单元,在控制UPR持续时间方面发挥着至关重要的作用.
- Rrp6介导的RNA处理对于及时停用UPR至关重要.
- 在ER压力期间Rrp6的下调是UPR解决的恒温机制.
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