Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism
Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism
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DOI：
10.1101/gad.423507
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发表时间：
2007-06-01
影响因子：
10.5
通讯作者：
Romby, Pascale
中科院分区：
文献类型：
--
作者：
Boisset, Sandrine;Geissmann, Thomas;Romby, Pascale
RNAIII是金黄色葡萄球菌群体感应系统的细胞内效应物。它是已知最大的调控rna之一（514个核苷酸长），可以控制大量毒力基因的表达。在这里，我们发现RNAIII的3'结构域在转录后水平上协同抑制编码一类毒力因子的mrna的表达，这些毒力因子在感染过程的早期起作用。我们证明，3'结构域主要作为反义RNA，并迅速退火到这些mrna，形成长RNA双链。RNAIII和mrna之间的相互作用抑制翻译起始并触发核糖核酸内切酶III水解。这些过程之后是mRNA库的快速耗尽。此外，我们发现RNAIII及其3'结构域通过涉及两个环环相互作用的有限数量的碱基配对介导rot mRNA的翻译抑制。由于Rot是一种转录调节蛋白，我们提出RNAIII间接作用于许多下游基因，从而激活几种外显蛋白的合成。这些数据强调了在建立金黄色葡萄球菌毒力因子网络时，RNAIII及其3'结构域所影响的众多调控步骤。
RNAIII is the intracellular effector of the quorum-sensing system in Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides long) that are known to control the expression of a large number of virulence genes. Here, we show that the 3' domain of RNAIII coordinately represses at the post- transcriptional level, the expression of mRNAs that encode a class of virulence factors that act early in the infection process. We demonstrate that the 3' domain acts primarily as an antisense RNA and rapidly anneals to these mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation and triggers endoribonuclease III hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In addition, we show that RNAIII and its 3' domain mediate translational repression of rot mRNA through a limited number of base pairings involving two loop-loop interactions. Since Rot is a transcriptional regulatory protein, we proposed that RNAIII indirectly acts on many downstream genes, resulting in the activation of the synthesis of several exoproteins. These data emphasize the multitude of regulatory steps affected by RNAIII and its 3' domain in establishing a network of S. aureus virulence factors.