Fig 8. Fe-S cluster assembly is regulated by multiple mechanisms in M. tuberculosis.

Rv1460 is transcribed independently from the operon allowing differential expression and regulation by the repressor. Initiation of translation is leaderless upstream of Rv1460, while a 5’-UTR containing a ribosome binding site regulates translation of Rv1461. The intein within Rv1461 must be resolved before it is functional and may represent an additional level of regulation of the system. Rv1460 is predicted to bind within the promoter region upstream of Rv1460 as well as within Rv1461 (as indicated by the dashed line boxes). Binding sites for other regulators within the Rv1460 promoter region and within the operon are also predicted, providing another level of regulation. Binding of an Fe-S cluster may change Rv1460’s affinity for DNA. Genes are not drawn to scale. The association of the Fe-S cluster machinery is inferred from other bacterial SUF systems, but has not been experimentally validated in mycobacteria. Cysteine is provided by the cysteine desulphurase, while the source of iron is unknown. The oligomeric state of Rv1460 is not indicated since it has not been confirmed, and the ratio of Fe-S cluster to Rv1460 protein is unknown.