EBV非编码RNA与新生RNA结合,将PAX5驱动到病毒DNA中
Nara Lee1, Walter N Moss1, Therese A Yario1
1Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
Cell
|February 10, 2015
概括
爱斯坦-巴尔病毒EBER2RNA引导PAX5转录因子进入病毒DNA. 这种相互作用对于调节病毒基因表达和复制至关重要,揭示了非编码RNA的新功能.
科学领域:
- 分子病毒学分子病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 非编码RNA生物学
背景情况:
- 爱斯坦-巴尔病毒 (EBV) 表达了丰富的核非编码RNA,EBER2.
- 之前,EBER2在宿主细胞核中的功能和定位尚不清楚.
- EBV基因组的终端重复 (TR) 是关键的调控区域.
研究的目的:
- 为了研究EBV EBER2 RNA的染色质定位.
- 阐明EBER2与转录因子PAX5.5之间的功能相互作用.
- 了解EBER2-PAX5相互作用在EBV基因调节和复制中的作用.
主要方法:
- 染色体,RNA和温度敏感免疫沉 (CHART) 来确定EBER2的基因组位置.
- 通过RNA免疫沉 (RIP) 来确认EBER2-PAX5相互作用.
- RNA干扰 (RNAi) 评估EBER2敲击对病毒基因表达和复制的功能影响.
- 来自TR位点的新生转录的分析,用于基配对相互作用.
主要成果:
- 图表显示EBER2局部化到EBV TRs,重叠PAX5结合点.
- EBER2与PAX5直接相互作用,对于其被TRs招募至关重要.
- 在EBER2中,EBER2 knockdown模仿PAX5的枯竭,提高LMP2A/B和LMP1的表达,并降低Lytic的复制.
- 招募是由EBER2基配对与新生的TR转录介导的,这是一个进化保守的机制.
结论:
- EBER2充当了支架,使用与新生RNA的基配对来招募PAX5到EBV TRs.
- 这种新型的RNA引导机制调节了关键的EBV潜伏基因和Lytic基因.
- 这些发现揭示了转录作用非编码RNA在引导转录因子到DNA点方面之前未被描述的功能.
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