Iron-sulfur (Fe-S) clusters are essential prosthetic groups involved in a myriad of cellular processes, including respiration, DNA repair, and immune defense. The biogenesis of Fe-S clusters is tightly regulated, with, in the model organism Escherichia coli, two Fe-S biogenesis machineries - ISC and SUF - operating under different conditions. While ISC ensures Fe-S cluster maturation under standard growth conditions, the less efficient SUF machinery intervenes during stress conditions like reactive oxygen species or iron limitation. This switch has significant physiological consequences, such as increased tolerance to certain antibiotics.
Recent studies have highlighted the critical role of small regulatory RNAs (sRNAs) in bacterial responses to stress, for example, in the activation of the SUF machinery under oxidative stress and iron starvation. Strikingly, recently published interactome datasets support a much larger post-transcriptional regulatory network centered around the ISC and SUF machineries.
This project aims to uncover a potential broader role for sRNAs in regulating Fe-S cluster biogenesis across diverse environmental conditions, beyond the well-established triggers like oxidative stress or iron limitation. Through bioinformatic analyses and experimental validation, the first objective is to identify novel interactions between sRNAs and mRNAs involved in Fe-S cluster biogenesis. By focusing on a selection of the most relevant regulatory interactions, mechanisms of action will be further investigated both in vitro and in vivo. Finally, the physiological impact of these regulations on bacterial adaptation to various stress conditions will be explored.
By unveiling this intricate regulatory network, this project will advance our understanding of Fe-S cluster biogenesis and shed light on the remarkable adaptability of bacteria to diverse environmental challenges.