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 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.
Boisset
Sandrine
S
Institut National pour la Recherche Médicale INSERM E0230, Université Lyon 1, Centre National de Référence des Staphylocoques, Faculté Laennec, Lyon, F-69008, France.
Geissmann
Thomas
T
Huntzinger
Eric
E
Fechter
Pierre
P
Bendridi
Nadia
N
Possedko
Maria
M
Chevalier
Clément
C
Helfer
Anne Catherine
AC
Benito
Yvonne
Y
Jacquier
Alain
A
Gaspin
Christine
C
Vandenesch
François
F
Romby
Pascale
P
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D006868:Hydrolysis; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D053038:Quorum Sensing; D016372:RNA, Antisense / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000235:genetics; D014158:Transcription, Genetic; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D001426:Bacterial Proteins; D016372:RNA, Antisense; D012329:RNA, Bacterial; D012333:RNA, Messenger; C096035:RNAIII, Staphylococcus aureus; D037521:Virulence Factors