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 Shawky1,2,3, Allison Scarboro1, Josef Mick1
1Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
bioRxiv : the preprint server for biology
|July 15, 2025
概括
死亡盒RNA螺旋酶DDX3X调节细胞中的mRNA翻译启动. 它促进或抑制特定mRNA的翻译,在细胞压力期间切换角色.
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
- 细胞应激反应的应激反应
背景情况:
- 在真核生物中,mRNA翻译启动对基因表达和细胞应激反应至关重要.
- 在mRNA 5' UTR扫描和启动编码子选择中,DEAD-box RNA螺旋酶DDX3X的确切功能尚不清楚.
- 了解DDX3X的作用对于理解细胞适应机制至关重要.
研究的目的:
- 在非压力和急性ER压力条件下阐明DDX3X在mRNA翻译启动中的作用.
- 研究DDX3X如何与mRNA相互作用并影响它们的翻译.
- 确定涉及DDX3X和转录后修改的新型监管机制.
主要方法:
- 分析DDX3X与eIF4F介导的48S扫描复合体内的数千个mRNA的接触.
- 对DDX3X对非压力细胞和急性ER压力细胞mRNA翻译的调控影响的比较评估.
- 识别特定的mRNA结合模式和相关的分子特征.
主要成果:
- DDX3X与众多mRNA结合,在非压力细胞中起到翻译促进剂和抑制剂的作用.
- 在急性ER压力期间,DDX3X逆转其对特定mRNA的调节功能.
- 明显的DDX3X结合模式与差异调节的mRNA相关,揭示了在起始码子附近的N4-乙化cytidines的联系.
结论:
- DDX3X在选择性mRNA翻译调节中发挥着关键的双重作用,这种调节是由细胞应激引起的.
- 在DDX3X介导调节下,在起始编码子附近的N4-乙化被确定为mRNA的特征.
- 这项研究揭示了RNA酶和mRNA修饰之间的新型相互作用,用于控制应激反应期间的翻译.
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