Figure 6.
A model for the multistep regulation of Fe-S cluster biogenesis. The expression of the genes involved in Fe-S cluster biogenesis and repair are fine-tuned in accordance with the cellular requirement both under normal growth and stress conditions. This effective regulation is maintained via the role of multiple redox-sensitive transcription factors: IscR, known to regulate both the isc and suf operons with its Fe-S cluster bound (holo-) and unbound (apo-) forms; OxyR, a global regulator that senses H2O2; Fur, which senses the availability of iron. Transcript level regulation of the housekeeping ISC machinery is executed by the small non-coding RNA, RhyB, that itself is under the control of the iron-deplete/ replete form of the Fur transcription factor. Under iron-replete conditions, holo-Fur inhibits the transcription of rhyB, but during iron starvation, apo-Fur increases and activates transcription of rhyB that binds to the isc transcript at the iscS Shine-Dalgarno locus leading to its degradation, leaving the iscR transcript intact due to the stability imparted by its secondary structure. This, in turn, increases apo-IscR, which then binds to the ORE-III sequence upstream of the suf operon. Arrow with black dotted border indicates reduced expression of the suf operon under reducing and iron-replete conditions.