Patrick Linder Group
Department of Microbiology and Molecular Medicine - Faculty of Medicine, University of Geneva
Project at a glance
RNA metabolism and control of gene expression in Staphylococcus aureus
Our group has a long-standing interest in the biological role of DEAD-box RNA helicase family proteins. These RNA helicases unwind short RNA duplexes, displace proteins from RNA, or function as regulated clamps on RNA.
They are therefore ideal players to control gene expression. After studying DEAD-box proteins in yeast for many years, our group is at present analysing RNA helicases in the opportunistic pathogen S. aureus. Our main focus is the analysis of two RNA helicases, CshA and CshB, and their role in virulence expression and adaptation to different growth conditions.
One of the helicases is required for mRNA turnover of certain RNAs, including the agr mRNA encoding a quorum sensing system. RNA deep-sequencing shows that approximately 5% of the RNAs are more stabilised in absence of the helicase. Present work aims at identifying the molecular signature of the RNAs that require CshA for efficient turnover and the role of this RNA helicase in helping the RNases to degrade the target molecules.
As an extension of this analysis, we are exploring the activities of the S. aureus RNases, that collaborate with CshA to degrade RNA. We have shown that RNase J1 and J2, which can cleave RNA both endonucleolyticalla and 5′ exonucleolytically, are crucial at sub-normal growth conditions. Apart from their role in RNA decay, these enzymes are also responsible for maturation of essential factors, such as 16S rRNA and RNase P RNA.
In parallel to the analysis of RNA metabolism, our laboratory is continuously developing or improving methods to genetically tackle this opportunistic pathogen. Doing so, we have inactivated a restriction system to allow efficient transformation in our clinical strain. We also developed a selection/counter-selection system that is very useful in creating deletions or genereplacements, even of genes that confer a very slow growth phenotype if inactivated.