人类分支点相互作用的干环序列和结构调节U2 snRNA表达,分支点识别和转录组
bioRxiv : the preprint server for biology
|September 5, 2025
概括
U2 snRNA中的分支点交互干环 (BSL) 影响结合体组合. 改变BSL结构会影响结合和基因表达,可能会激活癌症途径.
科学领域:
- 分子生物学
- 核糖核酸生物学
- 基因表达
背景情况:
- 结合体组合由U2小核核糖核蛋白 (snRNP) 引入内子开始,形成一个分支螺旋.
- 分支螺旋形成与U2 snRNA中的分支点相互作用干循环 (BSL) 相互排斥.
- 由于灵活的分支点序列,BSL结构在人体内合中的作用尚不清楚.
研究的目的:
- 研究BSL结构对人类内核中的U2 snRNP生物发生和拼接效率的影响.
- 检查扰乱BSL基配对对拼接和基因表达的影响.
- 通过改变BSL序列对U2 snRNA的表达进行转录组范围变化的分析.
主要方法:
- 使用直角U2 snRNA和拼接报告系统来研究BSL扰动.
- 评估了改变BSL基配对对U2 snRNA表达和记者拼接的影响.
- 进行全转录组分析以确定基因表达变化.
主要成果:
- 在BSL基配对的变化对U2 snRNA的表达和拼接效率产生了差异.
- 分枝点序列和U2 snRNA增强与野生类型和稳定BSL之间的高度互补性.
- 改变BSL或分支点识别序列导致类似的拼接和基因表达变化,包括瘤性通路的上调.
结论:
- 在初始合后,BSL结构会影响U2 snRNP生物发生,内子驱动BSL茎解.
- 改变的U2 snRNA变异被细胞容忍,但它们的存在会触发一种涉及癌症相关基因上调的反应.
- 这些发现突显了U2 snRNA结构对拼接的复杂调节及其对细胞反应和疾病途径的影响.
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