随着时间的推移,JNK激活动态驱动着不同的基因表达模式,由mRNA稳定性介导
bioRxiv : the preprint server for biology
|July 14, 2025
概括
细胞应激反应是由c-Jun N-终端激酶 (JNK) 动态调节的. 不同的JNK激活模式影响下游基因表达,影响细胞存活和炎症途径.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 系统生物学 系统生物学
背景情况:
- c-Jun N-终端激酶 (JNK) 对于调节细胞死亡至关重要.
- 在压力下,JNK动态影响细胞存活与细胞死亡的决策.
- 通过像c-Jun这样的转录因子,JNK动态与下游基因表达之间的联系需要进一步调查.
研究的目的:
- 研究特定的JNK激活动态 (持续,短暂,脉冲) 如何影响下游基因表达模式.
- 探索mRNA稳定性在调解基因表达对JNK动态反应中的作用.
- 确定由JNK动态差异调节的细胞通路.
主要方法:
- 利用JNK激动剂阿尼索米辛,诱导细胞中独特的JNK激活动态.
- 评估了由这些动态产生的下游基因表达模式.
- 采用普通微分方程 (ODE) 模型并测量mRNA衰变速率来分析基因表达调节.
- 在已识别的基因集群上进行了途径丰富分析.
主要成果:
- 观察到不同的基因表达模式,取决于JNK激活的特定动态.
- ODE模型表明mRNA稳定性介导这些基因表达集群的子集.
- 测量到的mRNA衰变速率支持了mRNA稳定的作用.
- 特定的基因集群在细胞死亡和炎症信号通路中得到了丰富.
结论:
- 简基因激活动态显著塑造下游基因表达模式.
- mRNA稳定性是影响基因表达对JNK信号传递反应的关键机制.
- 简基因动态有助于对关键细胞通路的差异调节,包括细胞死亡和炎症.
- 这些发现增加了对JNK信号如何控制细胞对压力的反应的理解.
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