含有odomain的蛋白4通过调节替代拼接来调节先天性炎症
Morgan W Mann1, Yao Fu1, Robert L Gearhart2
1Department of Medicine, University of Wisconsin - Madison, Madison, WI, United States.
Frontiers in immunology
|July 12, 2023
概括
含基因的蛋白4 (BRD4) 通过控制病毒感染期间的拼接因子表达来调节mRNA处理,包括免疫反应基因的替代拼接. 这揭示了BRD4在天生的免疫力中具有新的转录后作用.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 基因规则 基因规则
背景情况:
- 含有odomain的蛋白4 (BRD4) 是一个关键的转录调节器,参与癌症,炎症和纤维化.
- 众所周知,BRD4抑制剂 (BRD4i) 在病毒感染期间阻断促炎性细胞因子的释放.
- 尽管BRD4与结合体相互作用,但其转录后的调节作用在很大程度上仍未被探索.
研究的目的:
- 调查BRD4作为mRNA处理的调节器的假设.
- 阐明BRD4在病毒感染期间的转录后基因调节中的作用.
主要方法:
- 使用数据独立获取并行反应监测 (diaPASEF) 与RNA测序相结合.
- 分析了人类小气道上皮细胞的蛋白质和转录基因景观.
- 细胞受到病毒挑战,并用BRD4抑制剂治疗.
主要成果:
- 发现BRD4可以调节关键基因的替代拼接,例如与干扰素相关的发育调节器1 (IFRD1) 和X盒绑定蛋白1 (XBP1).
- 需要BRD4来表达氨酸-氨酸拼接因子和拼接体组件.
- BRD4 影响因诺西需要酶1 (IREα) 的表达,影响先天免疫反应和未折叠蛋白质反应 (UPR).
结论:
- BRD4在转录后RNA处理中起着重要作用,特别是调节替代拼接.
- BRD4控制了拼接因子的表达,从而影响病毒感染期间的先天免疫信号通路.
- 这些发现扩大了BRD4已知的功能,超越了转录延长,包括对mRNA处理的转录后调节.
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