一种新的HPV16拼接增强剂,对病毒瘤基因表达和细胞不朽化至关重要
Johanna Jönsson1, Lianqing Wang1,2, Naoko Kajitani1
1Department of Medical Biochemistry and Microbiology, Uppsala University, BMC-B9, 751 23 Uppsala, Sweden.
Nucleic acids research
|November 23, 2023
概括
研究人员在高风险的人类乳头瘤病毒 (HPV) 中发现了一种新的拼接增强剂. 这种增强剂对于产生E7蛋白和HPV16的产生至关重要.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 癌症研究 癌症研究
背景情况:
- 高风险的人类乳头瘤病毒 (HPV),如HPV16,利用瘤基因E6和E7进行致癌活性.
- 这些癌基因的表达来自替代拼接的信使RNA (mRNA).
- HPV16 E7 mRNA (E6*I/E7 mRNA) 的产生依赖于 SD226 和 SA409.9 拼接点之间的特定拼接事件.
研究的目的:
- 识别和描述控制HPV16 E6*I/E7mRNA拼接的调控元素.
- 研究一种新型拼接增强剂在HPV媒介癌症发生中的作用.
- 探索参与这种拼接调节的细胞因素.
主要方法:
- 拼接试验用于分析mRNA生产.
- 位点定向突变发生,以调查已识别的序列的功能.
- 细胞测试以评估对角质细胞不朽化的影响.
- 蛋白质结合实验以确定介导因素.
主要成果:
- 在HPV16 E6编码区域中发现了一种新的,富含腺素的拼接增强剂 (AAAAGCAAAGA重复).
- 这种增强剂中的突变特别抑制了E6*I/E7mRNA拼接.
- 这种抑制导致E7蛋白的产生减少,并取消了HPV16不朽化角质细胞的能力.
- 细胞蛋白TRAP150/THRAP3被确定为调解增强剂的活性,对高风险的HPVmRNA具有特异性.
结论:
- 在E6区域的一个新型,高风险的HPV特定拼接增强剂对HPV16的致癌潜力至关重要.
- 这种增强剂控制了E6*I/E7mRNA的产生,这对于E7蛋白表达至关重要.
- TRAP150/THRAP3调解了增强剂的功能,突出了HPV驱动癌症中的特定分子机制.
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