一个双的MAVS转录突出了一个类的截断变体在抗病毒免疫力中的类型
Sky W Brubaker1, Anna E Gauthier1, Eric W Mills2
1Division of Gastroenterology, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Cell
|February 18, 2014
概括
哺乳动物细胞使用多基斯特龙mRNA的替代翻译来调节先天免疫力. 对MAVS的双基斯特龙mRNA产生影响干扰素产生的一种变体,揭示了一种新的免疫控制层.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- 在细菌和病毒中常见的多基斯特龙信使RNA (mRNA) 允许从单个转录表达多种蛋白质.
- 这些多基斯特龙mRNA的替代翻译是产生蛋白质多样性和调节基因功能的已知的机制.
- 哺乳动物细胞中多基斯特龙信号的作用,特别是在调节复杂的生物过程中,如先天免疫力,是不太了解的.
研究的目的:
- 研究多基斯特龙mRNAs的替代翻译在调节哺乳动物细胞内天生的免疫信号传递中的作用.
- 确定和描述一个功能相关的多基斯特龙mRNA在抗病毒免疫中所涉及的具体例子.
- 探索多基斯特龙mRNAs在先天免疫系统中的潜在广泛参与.
主要方法:
- 用全基因组的核糖体概况分析来识别和分析翻译的多基斯特罗尼克mRNA.
- 进行了功能性测试,以评估不同蛋白质变体对干扰素生产和细胞死亡的影响.
- 特别研究了MAVS二基斯特龙mRNA及其编码蛋白 (全长MAVS和miniMAVS) 的表达和功能.
主要成果:
- 确定了一种编码抗病毒天生的免疫调节器MAVS (线粒体抗病毒信号蛋白) 的二基斯特龙mRNA和一个截断的变体miniMAVS.
- 发现miniMAVS变种干扰了由全长MAVS诱导的干扰素生产.
- 全长MAVS和小MAVS都积极调节细胞死亡途径.
- 核糖体分析发现了额外的抗病毒截断变体,这表明了一个更广泛的现象.
结论:
- 这项研究揭示了哺乳动物细胞中具有功能意义的二基斯特龙抗病毒mRNA,突出了替代翻译作为先天免疫的关键调节机制.
- 这些发现表明,多基斯特龙mRNA及其替代翻译产物在先天免疫系统中发挥的作用比以前估计的更为广泛.
- 迷你MAVS及其调节功能的发现为抗病毒信号通路的复杂性提供了新的见解.
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