由HSV-1延迟关联转录编码的微RNA的抗亡功能
A Gupta1, J J Gartner, P Sethupathy
1Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nature
|June 2, 2006
概括
简单疹病毒-1的延迟涉及一个由延迟关联转录 (LAT) 基因编码的微RNA (miRNA). 这种LAT小RNA通过调节TGF-β信号来保护受感染的神经元免受亡,帮助病毒的持久性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 微RNAs (miRNAs) 通过准信使RNAs (mRNAs) 来调节基因表达.
- 简单疹病毒-1 (HSV-1) 延迟相关转录 (LAT) 在神经元延迟期间表达,并促进感染细胞的存活.
- 通过LAT赋予抗亡性质的机制仍然是未知的.
研究的目的:
- 为了调查由HSV-1 LAT基因编码的miRNA是否有助于细胞灭绝抵抗.
- 为了识别和表征来自LAT基因的特定miRNA.
- 为了阐明LAT介导的亡抑制的机制.
主要方法:
- 用LAT基因片段感染神经母细胞瘤细胞.
- 细胞感染野生型和突变HSV-1菌株.
- 使用分子技术对miRNA表达的表征.
- 对亡标记物和TGF-β途径组件 (TGF-β 1,SMAD3) 的分析.
主要成果:
- 一种名为miR-LAT的miRNA在HSV-1 LAT基因的第一个前子中被确定.
- 表达LAT片段的细胞或感染野生型HSV-1的细胞显示出减少了细胞亡.
- 一种缺乏miR-LAT序列的突变HSV-1无法保护细胞免受亡.
- 据证明,miR-LAT可以降低转化生长因子 (TGF) -β1和SMAD3的表达.
结论:
- 在HSV-1 LAT基因编码一个miRNA (miR-LAT) 赋予抗亡.
- miR-LAT通过降低TGF-β信号通路的调节来抑制亡.
- 这种miRNA在维持HSV-1在感觉神经元中的延迟和持久性方面发挥着至关重要的作用.
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