Staphylococcus aureus; gene expression; RNA degradation; RNA helicase
Redder Peter (2016), How does sub-cellular localization affect the fate of bacterial mRNA?, in Current Genetics
, 62(4), 687-690.
Khemici Vanessa, Linder Patrick (2016), RNA helicases in bacteria, in Current Opinion in Microbiology
, 30, 58-66.
Prados J Linder P Redder P. (2016), TSS-EMOTE, a refined protocol for a more complete and less biased global mapping of transcription start sites in bacterial pathogens., in BMC Genomics.
, 17(1), 849.
Redder P., Hausmann S., Khemici V., Yasrebi H., Linder P. (2015), Bacterial versatility requires DEAD-box RNA helicases, in FEMS Microbiology Reviews
, 39(3), 392-412.
Khemici Vanessa, Prados Julien, Linder Patrick, Redder Peter (2015), Decay-Initiating Endoribonucleolytic Cleavage by RNase Y Is Kept under Tight Control via Sequence Preference and Sub-cellular Localisation, in PLOS Genetics
, 11(10), e1005577-e1005577.
Linder Patrick, Fuller-Pace Frances (2015), Happy birthday: 25 years of DEAD-box protein
, Springer New York, New York, NY.
Giraud Caroline, Hausmann Stéphane, Lemeille Sylvain, Prados Julien, Redder Peter, Linder Patrick (2015), The C-terminal region of the RNA helicase CshA is required for the interaction with the degradosome and turnover of bulk RNA in the opportunistic pathogen Staphylococcus aureus, in RNA Biology
, 12(6), 658-674.
Redder Peter (2015), Using EMOTE to map the exact 5'-ends of processed RNA on a transcriptome-wide scale
, Springer New York, New York, NY.
Linder Patrick, Lemeille Sylvain, Redder Peter (2014), Transcriptome-Wide Analyses of 5′-Ends in RNase J Mutants of a Gram-Positive Pathogen Reveal a Role in RNA Maturation, Regulation and Degradation, in PLoS Genetics
, 10(2), e1004207-e1004207.
Staphylococcus aureus is an opportunistic pathogen that can cause a variety of life threatening diseases. Many S. aureus strains harbor antibiotic resistance genes, but can also develop persistent infections that are phenotypically antibiotic resistant and very difficult to eradicate. The formation of biofilms and the phenotypic switching to small colony variants are two important strategies to cause persistent infections. Both, biofilm formation and intracellular survival of small colony variants, depend on the expression control of genes involved in these processes. The regulation of gene expression in bacteria can occur at several levels. In recent years small regulatory RNAs and the role of secondary structures have been recognized as important players in controlling gene expression. It is therefore likely that RNA helicases of the DEAD-box protein family function in local modulation of secondary structures or RNA-RNA unwinding to allow regulation of gene expression. Our published and preliminary data show that CshA, one of the two DEAD-box protein from S. aureus, participates in the turnover of RNA and thereby influences biofilm formation and hemolysis. Although this suggests that CshA participates together with RNases in the degradosome, the role of the helicase in this complex is unknown. Moreover, it is possible that CshA, like other bacterial DEAD-box proteins, performs additional functions in ribosome biogenesis or translation initiation, explaining some of the observed phenotypes in a cshA mutant. Preliminary results in the laboratory have shown that inactivation of the second RNA helicase, CshB, results in increased survival after an acid treatment and in a neutrophil killing assay. In addition, cshB mutant cells show a small colony variant phenotype after acid shock treatment. Finally, cshB mutants, but not wild type or ?cshA cells, are deficient for growth on a defined medium derived from a cell-culture medium. These different characteristics indicate an important role of CshB in gene expression. To learn more about the function of these two RNA helicases, we will search for their target molecules by cross-linking and immunoprecipitation of RNAs and polysome analysis, followed by RNA sequence analysis. To elucidate further the context in which these RNA helicases function and eventually how partner proteins influence their activity, we will also define interacting proteins. Finally, we will use genetic approaches to better define the processes in which these RNA helicase function. We will use suppressor analyses to identify genes that allow growth under non-permissive conditions and we will use saturated transposon mutagenesis to identify genes that - when mutated - enhance the helicase mutant phenotypes.