对异常的替代拼接和与年龄相关的感觉神经神经听力损失相关的RNA结合蛋白的综合分析
Wei Yu1, Zeping Qin2, XinYu Liang1
1Department of Otolaryngology, Head and Neck Surgery, Second Affiliated Hospital of Army Medical University, #183 Xinqiao Street, Shapingba District, Chongqing, 637000, People's Republic of China.
Scientific reports
|October 22, 2025
概括
RNA结合蛋白 (RBPs) 在与年龄相关的听力损失中驱动替代拼接事件. 这项研究确定了关键的RBP和拼接变化,揭示了感官神经听力损失 (SNHL) 的潜在治疗点.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
背景情况:
- 对于RNA结合蛋白 (RBPs) 在调节与年龄相关的感觉神经听力损失 (SNHL) 中的替代拼接 (AS) 的作用仍然基本上是未知的.
- 了解这些调节机制对于开发SNHL有效治疗至关重要.
研究的目的:
- 调查RBPs和AS在与年龄相关的SNHL中的参与.
- 识别与SNHL相关的特定放松管制的AS事件 (RASEs) 和差异表达的RBPs (DERBPs).
- 在DERBPs和RASEs之间构建监管网络.
主要方法:
- 综合分析来自老年性SNHL小鼠模型的RNA-seq数据.
- 识别RASE和DERBP的存在.
- 在DERBPs和RASEs之间建立监管网络.
- 使用人类多能干细胞衍生的巨细胞进行验证.
主要成果:
- 分别确定了198个和187个与严重和轻度SNHL症状相关的RASE.
- 发现了25个和14个与严重和轻度SNHL症状相关的DERBP.
- 在GTPase活动调节和细胞骨组织中发现了与RASE相关的基因的显著丰富.
- 证实ISG15作为关键拼接调节者的作用,直接影响人类细胞中UAP1替代拼接.
结论:
- 通过众多AS事件,RBPs在与年龄相关的SNHL的发病过程中发挥着重要作用.
- 识别的RBPs和AS事件代表了SNHL的潜在治疗标和生物标志物.
- 这项研究为与年龄相关的听力损失背后的分子机制提供了新的见解.
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