Coordination of the Fe-S cluster biogenesis network by the sRNA RyhB in E. coli

Iron (Fe) plays critical roles as enzyme cofactor involved in key biological processes but can also lead to toxicity by catalysing the formation of highly damaging reactive oxygen species. To stabilize Fe and perform catalysis, most organisms rely on Fe-S clusters, which are fundamental and evolutionary ancient cofactors. In E. coli, two distinct pathways for the biosynthesis of Fe-S cluster exist: the three-part iscR-SUA-hscBA-fdx-iscX (ISC-HSC) operon and the sufABCDSE (SUF) operon. The iscR-SUA section of the ISC-HSC operon is regulated at the promoter level by the IscR transcription factor and post-transcriptionally by the small RNA (sRNA) RyhB. The SUF operon is regulated by a combination of transcription factors, including the Fe-sensing Fur, the Fe-S using IscR, and the oxidative stress responsive OxyR. Here, we show evidence that the sRNA RyhB regulates the hscBA-fdx-iscX part of the ISC-HSC operon as well as part of the SUF operon. RyhB orchestrates a complex pattern of expression of the iscR-SUA-hscBA-fdx-iscX operon during Fe starvation. This results in increased level of iscR and constant expression of iscSUA, encoding the scaffold for Fe-S cluster formation. However, the third part of the operon, hscBA-fdx-iscX, encoding a chaperone that facilitates Fe-S cluster transfer, is repressed by RyhB during Fe starvation. Furthermore, RyhB represses part of the sufABCDSE transcript, which counteracts Fur derepression. Overall, RyhB represses both ISC and SUF systems under iron starvation, to reduce Fe-S biogenesis under such limiting conditions.