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保存的内部二次结构与隐藏的分支部位调节了毒素外子的替代拼接
Hao Li1, Zhan Ding1, Zhuo-Ya Fang1
1RNA Institute, State Key Laboratory of Virology, Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, TaiKang Center for Life and Medical Sciences, Wuhan University, Hubei 430072, China.
Nucleic acids research
|March 18, 2024
概括
RNA二次结构通过隐藏分支部位来调节替代拼接,影响基因表达和DNA修复. 这项研究揭示了涉及SF3B3的保存机制及其在基因组稳定中的作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 替代拼接 (AS) 产生多样化的RNA异型,增加蛋白质组复杂性.
- RNA二次结构在调节AS中的作用在很大程度上仍未被探索.
- 了解AS调节对于破译基因表达和细胞功能至关重要.
研究的目的:
- 研究RNA二次结构对替代拼接调节的贡献.
- 识别影响替代拼接事件的保存RNA结构,特别是毒素外子的包含.
- 阐明SF3B3在DNA修复中的生理功能.
主要方法:
- 系统的转录组分析,以预测隐藏分支部位的RNA二级结构.
- 细胞内SHAPE-MaP测试用于实验验证预测结构.
- RNA干扰屏用于识别相互作用的RNA结合蛋白.
- 基因组编辑以突变二级结构并评估DNA修复 in vivo.
主要成果:
- 在六种生物体中预测了成千上万的保存的二次结构与隐藏的分支地点.
- 在SF3B3基因中发现了一种保存的茎环结构,它调节毒素外子的包含和SF3B3的表达.
- 这种结构对U2因素敏感,其不稳定会改变SF3B3水平.
- 发现SF3B3通过增强ERCC6/CSB和RNA聚合酶II之间的相互作用来促进DNA修复.
- 细胞中二级结构的突变影响了体内DNA修复.
结论:
- RNA二次结构代表了一种新且常见的机制,用于调节毒素外子的替代拼接.
- SF3B3在DNA修复和基因组稳定性中发挥着关键作用,与其AS调节有关.
- 这项研究揭示了一种保存的调节机制,对基因表达和细胞功能有重大影响.
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