基因BRD2和BRD3独立进化了RNA结构,以控制非生产性拼接
Marina Petrova1, Sergey Margasyuk1, Margarita Vorobeva2
1Skolkovo Institute of Science and Technology, Bolshoy Bulvar, 30, str. 1, Moscow 121205, Russia.
NAR genomics and bioinformatics
|January 16, 2024
概括
哺乳动物的BRD2和BRD3基因使用毒素外子和RNA结构来控制非生产性拼接. 这种融合进化通过调节基因表达提供了治疗应用的潜力.
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 生物化学
背景情况:
- BRD2和BRD3是相关的原体和外端域 (BET) 蛋白质.
- BRD2的表达是通过涉及外子3b的非生产性剪接来调节的.
- 在BET蛋白中非生产性拼接机制尚未完全理解.
研究的目的:
- 研究BRD2和BRD3非生产性拼接的调节机制.
- 识别控制外子纳入的保存元素.
- 探索这些基因中的拼接调节的进化趋同.
主要方法:
- 生物信息分析以确定保护的互补区域 (PCCR).
- 微基因突变发生,以研究外基因包容性.
- 反感性寡核酸以探测RNA结构的参与.
- 在不同条件下分析基因表达和拼接模式.
主要成果:
- 在BRD2和BRD3内子中确定了PCCRs,调节毒素外子的包含.
- 证明RNA结构决定了毒素外型子的包容率.
- 观察到BRD2和BRD3表达的下调,在毒素外子被包含时.
- 表明转录延长减缓会影响毒素外子跳转.
结论:
- BRD2和BRD3独立获得了用于拼接控制的毒素外子和RNA结构.
- PCCRs在调节非生产性拼接方面发挥着至关重要的作用.
- 观察到拼接调节机制的趋同演变.
- 这些发现对BET蛋白表达的向治疗调节有意义.
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