跨王国模仿是小病毒激酶对核糖体进行定制的基础
Sujata Jha1, Madeline G Rollins1, Gabriele Fuchs2
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Nature
|June 22, 2017
概括
脊髓灰质炎病毒通过化RACK1蛋白质来劫持宿主核糖体,改变其结构以有利于病毒RNA的转化. 这种跨王国模拟使病毒能够利用RNA聚合酶错误进行复制.
科学领域:
- 分子生物学
- 病毒学
- 结构生物学
背景情况:
- 核糖体通过识别特定的RNA元素来调节基因表达.
- 在单个细胞内调节核糖体专业化的证据有限.
- 众所周知,天花病毒可以操纵宿主细胞机械进行复制.
研究的目的:
- 研究小病毒控制翻译的机制.
- 识别涉及毒病毒RNA翻译的特定宿主因素.
- 阐明病毒RNA元素是如何被宿主核糖体识别的.
主要方法:
- 人类小核糖体子单元蛋白RACK1 (活性C激酶受体) 的酸化分析.
- 对RACK1进行结构和遗传学分析.
- 用模仿剂和跨物种的仿真物来评估RACK1的功能.
主要成果:
- 在人类RACK1中,异于未感染或其他病毒感染的细胞,Poxvirus激酶化特定的血清/三氨酸残留物.
- RACK1的酸化选择了含有多A导体的病毒mRNA的翻译 (腺重复).
- 当RACK1的变量循环负电荷时 (类似植物),就决定了对病毒RNA的核糖体选择性.
结论:
- 脊髓灰质炎病毒通过RACK1酸化重塑宿主核糖体,从而形成类似植物的状态.
- 这种修改使病毒RNA与多A导体的翻译成为可能,利用RNA聚合酶滑动错误.
- 通过跨王国模拟和特定物种的RNA领导活动,发现了核糖体定制.
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