在RBMS1-引起的ANKRD1稳定介导的早期衰老中增加ANKRD1水平
Chang Hoon Shin1, Martina Rossi1, Carlos Anerillas1
1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
Molecular and cellular biology
|May 21, 2024
概括
细胞衰老涉及增加的ANKRD1蛋白质. RNA结合蛋白RBMS1稳定ANKRD1mRNA,在早期衰老过程中增加其产量.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 基因规则 基因规则
- 衰老研究研究 衰老研究
背景情况:
- 细胞衰老是一种不可逆转的细胞循环停止状态.
- 在衰老过程中,ANKRD1 (ankyrin重复域1) 蛋白质水平增加.
- 在早期衰老中调节ANKRD1生产的机制尚未完全理解.
研究的目的:
- 阐明驱动早期衰老中ANKRD1产量升高的机制.
- 为了识别与ANKRD1 mRNA相互作用的蛋白质.
- 调查 RBMS1 在 ANKRD1 监管中的作用.
主要方法:
- 乙氧化物 (Eto) 治疗以诱导纤维细胞的衰老.
- 对ANKRD1mRNA和蛋白质水平的分析.
- 反意义寡合体 (ASO) 拉向和质谱学.
- 核糖蛋白免疫沉降 (RIP) 分析.
- RBMS1沉默和过度表达的研究.
- 记者基因测试. 记者基因测试.
主要成果:
- 通过中度的转录/翻译和强大的mRNA稳定,乙氧化物诱导的衰老增加了ANKRD1.
- RBMS1 特别结合到 ANKRD1 mRNA.
- 在衰老过程中,RBMS1的细胞定位从核转移到细胞质.
- RBMS1 枯竭减少了 ANKRD1 mRNA 半衰期; RBMS1 的过度表达增强了它.
- 一个特定的ANKRD1mRNA区域中介于RBMS1的结合和表达.
结论:
- 在早期的化物诱导衰老期间,RBMS1稳定ANKRD1mRNA.
- RBMS1在ANKRD1.1的转录后调节中发挥着关键作用.
- 这种机制导致老化细胞中ANKRD1水平升高.
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