切割部位偏好允许流感A病毒PA-X区分宿主和病毒mRNA
Lea Gaucherand1,2,3, Amrita Iyer2, Isabel Gilabert2,4
1Program in Molecular Microbiology, Tufts University Graduate School of Biomedical Sciences, Boston, MA, USA.
Nature microbiology
|June 22, 2023
概括
流感A病毒PA-X内核酶降解宿主RNA以帮助病毒复制. 它优先将GCUG四分体切割成RNA毛针环,从而区分宿主和病毒遗传物质.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 基因表达 基因表达
背景情况:
- 病毒经常抑制宿主基因表达 (宿主关闭),以促进复制.
- 通过内啡核酶降解RNA是一种常见的宿主关闭机制.
- 流感A病毒PA-X内核酶节省病毒RNA,同时降解宿主RNA.
研究的目的:
- 为了阐明PA-X裂变的RNA序列和结构决定因素.
- 了解PA-X如何区分宿主和病毒RNA.
主要方法:
- 用5'快速放大互补DNA末端与高通量测序 (5'RACE-Seq) 相结合,对PA-X分裂部位进行全转录组特征化.
- 预测RNA结构和报告测试以验证分离偏好.
- 在A型流感病毒基因组内进行体内选择实验.
主要成果:
- PA-X 首选在位于发针环内的 GCUG 四分体上切割 RNA.
- 与流感病毒转录组相比,GCUG四分体在人类转录组中显著丰富.
- 流感A病毒在被引入其基因组时迅速选择最佳的PA-X切割点.
结论:
- PA-X对RNA裂变表现出序列和结构偏好,准头环中的GCUG四分体.
- 这些偏好使PA-X能够对病毒RNA进行歧视,避免其降解.
- PA-X的裂变特征表明了针对宿主mRNA而不是病毒mRNA的进化机制,类似于自我/非自我歧视.
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