一个snoRNA-tRNA修饰网络控制着编码子偏差的细胞状态
Minjie Zhang1, Kongpan Li1, Jianhui Bai1
1Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089.
概括
这项研究揭示了小核RNA (snoRNA) 如何调节tRNA的修饰,从而影响细胞状态. 失去特定的snoRNAs (D97/D133) 将细胞从增殖转移到发育,因为它改变了代码的使用.
科学领域:
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
- 细胞的新陈代谢
背景情况:
- 对于细胞翻译来说,tRNA供应和编码子需求之间的平衡至关重要.
- 这种平衡的精确监管机制和功能结果尚未完全理解.
- 已知小核RNAs (snoRNAs) 可以修改核糖体RNA,但它们在tRNA修改中的作用不太清楚.
研究的目的:
- 阐明snoRNAs在细胞翻译中的目标和功能.
- 研究snoRNAs在tRNA修饰中的作用及其对细胞状态的影响.
- 解决孤儿snoRNA及其对翻译经济的贡献的.
主要方法:
- 在PARIS2交互原子捕获中.
- 结构建模 结构建模
- 保护分析 保护分析
- RNA-蛋白相互作用分析
- 修改映射中的修改映射
- 在HEK293细胞和小鼠胚胎干细胞中进行CRISPR-Cas9基因编辑 (Knockout/Knockdown).
主要成果:
- 确定了全球tRNA修饰 (包括2'-O-甲基化) 所必需的snoRNA-tRNA相互作用网络.
- 证明了失去了snoRNAs D97/D133导致了目标tRNA水平的降低和编码子的适应.
- 表明D97/D133淘汰会抑制与繁殖相关的基因程序,并促进与人类和小鼠细胞的发展相关的程序.
结论:
- snoRNAs在调节tRNA修饰和细胞命运方面发挥着至关重要的作用.
- D97/D133snoRNAs是氨酸tRNA修饰的关键调节者,影响增殖和发育之间的平衡.
- 这项工作揭示了snoRNAs在控制子偏差细胞状态方面的新功能.
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