在急性ER应激中,DDX3X作为mRNA翻译的选择性双开关调节器
Abd-El Monsif A Shawky1, Allison V Eckhardt2, Josef B Mick2
1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA; Department of Cell Biology, Biotechnology Research Institute, National Research Centre, Giza 12622, Egypt.
Cell reports
|October 30, 2025
概括
死亡盒RNA螺旋酶DDX3X通过调节mRNA翻译启动来微调基因表达. 它在受压力和非压力细胞中的作用不同,可能与RNA修饰有关.
科学领域:
- 分子生物学分子生物学
- 基因表达规范 基因表达规范
- 在RNA生物学,RNA生物学.
背景情况:
- 细胞mRNA的翻译启动对于基因表达和细胞应激反应至关重要.
- 在不同的细胞条件下,DEAD-box RNA基酶DDX3X在翻译调节中的作用尚未完全被理解.
研究的目的:
- 阐明DDX3X在正常细胞和应激细胞的mRNA翻译启动中的精确功能.
- 调查DDX3X与表皮转录组修饰的调节机制和潜在联系.
主要方法:
- 在eIF4F介导的48S扫描复合体内分析DDX3X与mRNA的关联.
- 启动配置文件,在mRNA 5' UTR和编码序列中映射DDX3X结合模式.
- 研究DDX3X调节的mRNA与cytidine N4-乙化之间的关系,包括NAT10敲击实验.
主要成果:
- 作为48S扫描复合体的一部分,DDX3X与众多mRNA相互作用.
- 在基底条件下,DDX3X表现出双重作用,促进或抑制翻译,在内质网膜应激过程中效果逆转.
- 机械上不同的DDX3X作用模式与其结合部位相关.
- 调节DDX3X的mRNAs显示在启动编码子附近的特定的cytidine N4-乙化模式,其中NAT10的淘汰会影响de-repression.
结论:
- DDX3X作为mRNA翻译启动的上下文依赖调节器.
- DDX3X的调节功能是由细胞应激调节的.
- 在DDX3X介导的翻译控制和表皮转录学特征之间存在潜在的功能联系,特别是cytidine N4-乙化.
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