替代分离法规对最大寿命的影响
Wei Jiang1, Sika Zheng2,3, Liang Chen1
1Department of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
哺乳动物中的替代拼接 (AS) 模式揭示了与最大寿命 (MLS) 相关的独特分子机制. 这些与寿命相关的AS事件,特别是在大脑中,为超越基因表达的长寿提供了新的见解.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 哺乳动物的最大寿命 (MLS) 呈现出百倍以上的变化.
- 这种寿命多样性的分子基础尚未完全理解.
- 替代拼接 (AS) 是基因功能的一个关键调节器.
研究的目的:
- 调查保存的替代拼接事件在哺乳动物最大寿命中的作用.
- 为了比较不同组织中的AS模式及其与MLS的关联.
- 探索AS,基因表达,身体质量和衰老之间的关系.
主要方法:
- 在26种哺乳动物物种中对6种组织进行替代拼接的跨物种分析.
- 识别与MLS显著相关的保存的AS事件.
- 与MLS相关的AS事件与基因表达和体重相关性的比较.
- 在MLS和与年龄相关的AS事件中分析RNA结合蛋白质基因协调.
主要成果:
- 确定了数百个保存的AS事件,并且与MLS有显著的关联.
- 大脑显示,与外围组织相比,组织特异性MLS相关的AS事件的患病率更高.
- MLS-AS事件与mRNA处理,应激反应,神经元功能和表观遗传学相关的途径丰富,与表达水平相关性不同.
- 与MLS相关的AS事件表现出更强的RNA结合蛋白质基因协调,这表明编程寿命适应.
结论:
- 替代拼接代表了一个独特的,转录独立的机制,调节哺乳动物的寿命.
- 与MLS相关的AS事件为长寿提供了独特的见解,特别是在神经组织中.
- 这些发现突出了AS作为哺乳动物进化和寿命的决定的一个关键因素.
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