卡斯巴酶介导的TRBP处理在病毒感染期间调节了细胞亡
Keiko Shibata1, Harune Moriizumi1, Koji Onomoto2
1Department of Biochemistry and Molecular Biology, Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
Nucleic acids research
|April 18, 2024
概括
在病毒感染期间,TARRNA结合蛋白 (TRBP) 的功能发生转变. 最初促进RNA沉默,它后来诱导了亡,并通过碎片化抑制干扰素信号,影响病毒防御机制.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 由microRNAs (miRNAs) 介导的RNA沉默对于基因调节至关重要.
- 在病毒感染期间RNA沉默机制的作用仍然不完全理解.
- TARRNA结合蛋白 (TRBP) 通过Dicer相互作用增强了miRNA的成熟.
研究的目的:
- 阐明TRBP在病毒感染期间的调节作用.
- 为了研究TRBP在病毒感染晚期阶段的功能转化.
- 了解TRBP处理如何影响细胞亡和干扰素信号传递.
主要方法:
- 研究了TRBP与病毒传感器蛋白LGP2.2的相互作用.
- 在病毒感染期间分析了 caspases 的 TRBP 处理.
- 研究了TRBP碎片与Dicer和干扰素信号调节器 (PKR,LGP2) 的相互作用.
- 评估TRBP处理对亡和干扰素信号传递的影响.
主要成果:
- 在早期病毒感染中,TRBP与LGP2相互作用,抑制miRNA成熟并诱导亡.
- 病毒感染激活卡斯帕斯,将TRBP切割成N端和C端碎片.
- N端TRBP片段与PKR和LGP2相互作用,诱导ER压力和亡.
- TRBP处理抑制了I型干扰素的信号传递,导致不可逆转的亡.
结论:
- 在病毒感染期间,TRBP经历了功能转换,从miRNA成熟转向诱导亡.
- 卡斯帕斯的TRBP处理是增强亡和抑制干扰素反应的关键机制.
- 这项研究揭示了TRBP在病毒病原和免疫逃避中的新作用.
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