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hnRNP H通过GGG动机控制人类乳头瘤病毒16型E1,E6,E7和E6^E7mRNA的替代拼接
Johanna Jönsson1, Qiaoli Zhai1,2, Stefan Schwartz1
1Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Journal of virology
|September 17, 2024
概括
异质核核核糖核蛋白 (hnRNP) H 结合HPV16拼接部位,调节基因表达. 这种相互作用控制了E6^E7融合蛋白水平,可能影响HPV16驱动的癌症.
科学领域:
- 分子病毒学分子病毒学
- 关于RNA分离的规定
- 癌症生物学 癌症生物学
背景情况:
- 人类乳头瘤病毒16型 (HPV16) 基因mRNAs (E6和E7) 经历复杂的替代RNA剪接.
- 替代拼接对于产生病毒coproteins至关重要,这些蛋白质有助于HPV16诱导的致癌.
- 特定的拼接部位,如SD880,以及调节因素是控制HPV16基因表达的关键.
研究的目的:
- 研究异质核核核糖核蛋白 (hnRNP) H在调节HPV16替代RNA剪接中的作用.
- 阐明 hnRNP H 与 HPV16 拼接部位相互作用以控制瘤基因 mRNA 生产的机制.
- 确定hNRNP H对HPV16E6,E7和E6^E7蛋白的表达水平的影响.
主要方法:
- 在感染HPV16的细胞中分析RNA拼接模式.
- 确定与HPV16 SD880拼接部位相邻的hNRNP H结合部位 (GGG动机).
- 试验操纵hNRNPH水平以评估其对HPV16mRNA和蛋白质生产的影响.
主要成果:
- hnRNP H与HPV16拼接部位SD880附近的GGG基因结合,促进到SA742部位的拼接.
- 这种相互作用增强了E6^E7融合蛋白mRNA的产生,而牺牲了其他拼接变体.
- hnRNP H 过度表达还通过促进内子保留来增加 E1 蛋白质的产生.
结论:
- hnRNP H是HPV16基因表达程序的关键调节者,控制着coprotein生产的平衡.
- 聚变蛋白E6^E7,其产生受 hnRNP H 的调节,稳定HPV16 coproteins.
- hnRNP H代表了针对HPV16感染的抗病毒药物开发的潜在治疗标.
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