In the bacterial cell, the level of a given mRNA, and thus the potential for protein expression, is determined by two main factors: Transcription and RNA decay. The machinery for transcription initiation and elongation is highly conserved across bacterial phyla, whereas the decay machinery, although always extremely efficient, is fundamentally different between for example Escherichia coli and Staphylococcus aureus. In the former, RNA decay is initiated by RNase E, which performs an endo-ribonucleolytic cleavage that serves as entry-point for 3' to 5' exo-ribonucleases. In contrast, S. aureus and many other Gram-positive pathogens do not have an RNase E homolog, but instead encode the endo-ribonuclease RNase Y, and the 5’ to 3’ exoribonucleases RNase J1 and RNase J2.
Our research is at the cross-road between the disciplines of genetics, microbiology, bioinformatics and biochemistry. By using a combination of classic methods, such as Northern blotting and allelic replacement, and modern techniques, such as Next-Generation Sequencing and in vivo localisation microscopy, we are able to discover additional levels of gene-regulation rooted in RNA decay, and discern the networks of interactions that control this, ensuring that RNA degradation neither goes too fast, nor too slow.
We mainly focus on Firmicutes, specifically Staphylococcus aureus, where we have developed the required genetic and biological tools, and where modifications in gene regulation often impacts human health. We examine the in vivo activity and molecular mechanisms of RNase J1 and J2 (among others), and map their cleavages with nucleotide precision and on a global scale, ii) uncover how the sequence-information of an RNA determines its half-life, and iii) examine spacial relationship between RNases and their RNA targets, in the intra-cellular space.
- Ardissone S, Redder P, Russo G, Frandi A, Fumeaux C, Patrignani A, Schlapbach R, Falquet L, Viollier PH.
Cell Cycle Constraints and Environmental Control of Local DNA Hypomethylation in α-Proteobacteria
- Prados J, Linder P, Redder P..
TSS-EMOTE, a refined protocol for a more complete and less biased global mapping of transcription start sites in bacterial pathogens.
- Armitano J, Redder P, Guimarães VA, Linder P..
An Essential Factor for High Mg(2+) Tolerance of Staphylococcus aureus
Frontiers in Microbiology