通过内部RNA结构控制基因输出
Leonard Schärfen1,2, Pernille Bech1, Paulina Podszywałow-Bartnicka1
1Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT 06520, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
内部RNA结构通过调节mRNA前拼接,显著影响基因表达. 修改内部基配对可以提高拼接效率和微调基因输出.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物信息学是一种生物信息学.
背景情况:
- 预mRNA剪接删除了内子,这是真核生物基因表达的一个关键步骤.
- 内核突变可以导致遗传疾病,但除了拼接部位之外的内核序列的作用尚不清楚.
- 内子内的RNA结构可能会影响拼接效率和基因输出.
研究的目的:
- 系统地研究内部RNA结构的形成如何调节基因输出.
- 为了确定基配对在自然内子的每个位置对拼接的影响.
- 探索设计内部变化的潜力,以提高拼接效率.
主要方法:
- 创建内部变体库,以测试基因配对影响.
- 大规模并行报告测试 (MPRA) 用于测量拼接调制.
- 热力学结构预测和机器学习模型来解释基因输出.
主要成果:
- 涉及拼接点的基配对显著调节了跨数量级的拼接.
- 一个上游的内部区域对结构的敏感性表明了硬质障碍.
- 机器学习模型根据RNA结构准确预测基因输出.
- 设计的内部序列改变改善了人类β-环球蛋白IVS1.1.的低效拼接.
结论:
- 内部RNA结构是基因表达的关键调节者.
- 调节内子基配对提供了一种微调基因输出和纠正拼接缺陷的策略.
- 在进化过程中,改变RNA结构的内部突变被快速选择.
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