sigR

SigR is an extracytoplasmic function (ECF) sigma factor found in several actinobacteria, most notably Streptomyces species. It orchestrates the transcriptional response to thiol-oxidative stress by directing RNA polymerase to a set of oxidative stress–responsive genes, collectively known as the SigR regulon. Activation of SigR helps the cell adapt to redox imbalance and protects against damage from reactive oxygen species.

The activity of SigR is tightly regulated by an anti-sigma factor, RsrA. In reducing conditions, RsrA binds SigR and prevents transcription. Upon thiol-oxidative stress, RsrA forms disulfide bonds and releases SigR, allowing SigR to bind RNA polymerase and initiate transcription of target genes. These targets typically include components of the thioredoxin system and other redox-balancing proteins that maintain protein folding and repair mechanisms. As redox homeostasis is restored, reducing conditions promote the re-association of RsrA with SigR, turning off the response.

SigR regulation contributes to cellular resilience by enabling rapid adaptation to oxidative challenges and, in some species, influencing secondary metabolism and antibiotic production through interconnected stress response networks. The SigR–RsrA system is widely studied as a model of redox-responsive transcriptional control in bacteria and is observed in multiple actinobacterial genomes, often with nearby rsrA genes that encode the anti-sigma factor.

Overall, SigR functions as a key regulator of oxidative stress responses, balancing protective gene expression with regulatory feedback to restore cellular redox balance.