title: Dual RNA regulatory control of a Staphylococcus aureus virulence factor.
abstract: 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.
authors: Université de Rennes 1, Inserm U835-UPRES EA 2311, Biochimie Pharmaceutique, 2 avenue du Prof. Léon Bernard, 35043 Rennes, France.
authors: Svetlana
authors: S
authors: Chabelskaya
authors: Valérie
authors: V
authors: Bordeau
authors: Brice
authors: B
authors: Felden
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D009690:Nucleic Acid Conformation; D010442:Peptide Chain Initiation, Translational; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012270:Ribosomes / Q000378:metabolism; D013211:Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D012329:RNA, Bacterial; D012333:RNA, Messenger; C096035:RNAIII, Staphylococcus aureus; D038621:Regulatory Sequences, Ribonucleic Acid; C112405:Sbi protein, Staphylococcus aureus; D037521:Virulence Factors