由细菌毛孔形成毒素诱导的替代拼接加剧了CIRBP介导的细胞对Listeria感染的反应
Morgane Corre1, Volker Boehm2,3, Vinko Besic1
1Group Bacterial infection, response & dynamics, Institut de biologie de l'ENS (IBENS), École normale supérieure, CNRS, INSERM, Université PSL, 75005 Paris, France.
Nucleic acids research
|November 9, 2023
概括
被Listeria monocytogenes感染的肠道细胞通过切换到特定的RNA异型来改变基因表达. 这调节了细菌感染,影响了宿主细胞的防御机制.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 细胞对细胞内细菌的反应涉及显著的基因表达变化.
- 了解异形级调节对于详细分析这些反应至关重要.
研究的目的:
- 在Listeria monocytogenes感染期间研究肠道上皮细胞的异形水平调节.
- 阐明替代拼接在细胞防御细菌病原体中的作用.
主要方法:
- 结合感染肠道上皮细胞的长读和短读转录组分析.
- 研究了细菌毛孔形成毒素对剪接因子酸化和活性的影响.
- 分析了特定的CIRBP异型使用对细菌负载的功能后果.
主要成果:
- CIRBP (冷诱导性RNA结合蛋白) 和SRSF (氨酸/氨酸丰富的剪接因子) 的表达转向无意义介导的衰变敏感异型.
- 细菌毒素通过抑制CLK1激酶诱导SRSF脱化,促进CIRBP替代拼接.
- 特定的CIRBP异型表达调节了细胞内细菌负载,正规的CIRBP减少了它,而毒素外形异型则加剧了它.
结论:
- CIRBP和SRSF的替代拼接是对细菌感染的关键细胞反应.
- 这种机制涉及毒素诱导的剪接因子修饰,影响宿主对利斯特菌的防御.
- 研究结果将替代拼接概括为一种适用于细菌病原性的常见应激反应.
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