Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism

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 repr...

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Published in:	Genes & development Vol. 21; no. 11; pp. 1353 - 1366
Main Authors:	Boisset, Sandrine, Geissmann, Thomas, Huntzinger, Eric, Fechter, Pierre, Bendridi, Nadia, Possedko, Maria, Chevalier, Clément, Helfer, Anne Catherine, Benito, Yvonne, Jacquier, Alain, Gaspin, Christine, Vandenesch, François, Romby, Pascale
Format:	Journal Article
Language:	English
Published:	United States Cold Spring Harbor Laboratory Press 01-06-2007
Subjects:	3' Untranslated Regions 3' Untranslated Regions - genetics 3' Untranslated Regions - metabolism Bacterial Proteins Bacterial Proteins - genetics Bacterial Proteins - metabolism Base Sequence Biochemistry, Molecular Biology Gene Expression Regulation, Bacterial Hydrolysis Life Sciences Molecular Sequence Data Nucleic Acid Conformation Quorum Sensing Research Paper RNA, Antisense RNA, Antisense - chemistry RNA, Antisense - genetics RNA, Antisense - metabolism RNA, Antisense - pharmacology RNA, Bacterial RNA, Bacterial - chemistry RNA, Bacterial - genetics RNA, Bacterial - metabolism RNA, Messenger RNA, Messenger - genetics RNA, Messenger - metabolism Sequence Homology, Nucleic Acid Staphylococcus aureus Staphylococcus aureus - enzymology Staphylococcus aureus - genetics Transcription, Genetic Virulence Factors Virulence Factors - genetics Virulence Factors - metabolism translational repression antisense regulation virulence Staphylococcus aureus Regulatory RNA RNase III
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC1877748 These authors contributed equally to this work.
ISSN:	0890-9369 1549-5477
DOI:	10.1101/gad.423507