通过SRSF7的下调,通过产生MDM2变体,诱导细胞衰老
Jiwon Hong1,2,3, Seongki Min1,2,3, Gyesoon Yoon1,2,3
1Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea.
Aging
|December 30, 2023
概括
降低SRSF7的调节会通过改变MDM2.2的替代拼接来触发细胞衰老. 这导致p53稳定,并形成诱导衰老的MDM2变体,突出SRSF7.
科学领域:
- 分子生物学分子生物学
- 细胞衰老 细胞衰老
- 在RNA分离过程中.
背景情况:
- 替代拼接 (AS) 从单一的前mRNA产生多种不同的蛋白质变体.
- 改变的AS越来越被认为是细胞衰老和衰老的因素.
- 参与衰老调节的特定AS变异在很大程度上是未知的.
研究的目的:
- 识别老化的AS变体并阐明它们的监管作用.
- 为了研究SRSF7在细胞衰老中的功能.
- 为了确定SRSF7,MDM2剪接和p53-介导衰老之间的联系.
主要方法:
- 从体外衰老模型中分析RNA-seq和微阵列数据集.
- 在人体双胞胎纤维细胞 (HDFs) 中进行SRSF7敲除实验.
- 验证mRNA和蛋白质水平,稳定p53和MDM2变体的形成.
- 对MDM2-C AS变体的识别和功能验证.
主要成果:
- 在衰老细胞中,SRSF7的下调常见.
- 在HDF中,SRSF7敲除诱导衰老,p53稳定和MDM2变体形成.
- MDM2-C被确定为一个关键的功能性AS变体,专门由SRSF7枯竭产生的.
- 在HDF中,MDM2-C过度表达导致老化.
结论:
- SRSF7下调是p53介导衰老的一个关键事件.
- SRSF7调节MDM2的替代拼接,这是p53.3的一个关键负调节器.
- 鉴定到的MDM2-C变体在诱导细胞衰老方面发挥着重要作用.
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