Dual RNA regulatory control of a Staphylococcus aureus virulence factor.

Dual RNA regulatory control of a Staphylococcus aureus virulence factor.
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DOI:
10.1093/nar/gku119
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发表时间:
2014-04
影响因子:
14.9
通讯作者:
Felden B
Felden B
中科院分区:
生物学2区
文献类型:
--
作者:
Chabelskaya S;Bordeau V;Felden B

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在病原体中,毒力基因表达的精确编程对于感染是必不可少的。它是由复杂的调控蛋白和核糖核酸(sRNA)阵列实现的,但在许多情况下,它们的贡献和连接尚不清楚。基于遗传,生化和结构的证据,我们报告说,表达模式的金黄色葡萄球菌宿主免疫逃避蛋白是由RNAIII和小致病岛RNA D(SprD)的协同作用。它们在细菌生长期间的组合表达谱允许Sbi的早期和瞬时合成以避免宿主免疫应答。这两种sRNA一起使用反义机制在翻译水平上监测Sbi表达。缺失分析结合RNAIII与其新的信使RNA(mRNA)的目标复合物的结构分析表明,三个遥远的RNAIII域与不同的网站的sbi mRNA的相互作用,两个位置是深的sbi编码区。通过不同的结构域,RNAIII降低了避免先天宿主免疫所需的两种蛋白质的产生,即葡萄球菌蛋白A和Sbi。足印和体内突变分析揭示了一种新的监管模块RNAIII内的Sbi翻译衰减必不可少的。两种差异表达的sRNA对mRNA的复杂翻译控制确保了主要病原体对宿主免疫逃逸的监督。
In pathogens, the accurate programming of virulence gene expression is essential for infection. It is achieved by sophisticated arrays of regulatory proteins and ribonucleic acids (sRNAs), but in many cases their contributions and connections are not yet known. Based on genetic, biochemical and structural evidence, we report that the expression pattern of a Staphylococcus aureus host immune evasion protein is enabled by the collaborative actions of RNAIII and small pathogenicity island RNA D (SprD). Their combined expression profiles during bacterial growth permit early and transient synthesis of Sbi to avoid host immune responses. Together, these two sRNAs use antisense mechanisms to monitor Sbi expression at the translational level. Deletion analysis combined with structural analysis of RNAIII in complex with its novel messenger RNA (mRNA) target indicate that three distant RNAIII domains interact with distinct sites of the sbi mRNA and that two locations are deep in the sbi coding region. Through distinct domains, RNAIII lowers production of two proteins required for avoiding innate host immunity, staphylococcal protein A and Sbi. Toeprints and in vivo mutational analysis reveal a novel regulatory module within RNAIII essential for attenuation of Sbi translation. The sophisticated translational control of mRNA by two differentially expressed sRNAs ensures supervision of host immune escape by a major pathogen.
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