Inverse regulation of Fe- and Ni-containing SOD genes by a Fur family regulator Nur through small RNA processed from 3′UTR of the sodF mRNA

Superoxide dismutases (SODs) are widely distributed enzymes that convert superoxides to hydrogen peroxide and molecular oxygen, using various metals as cofactors. Many actinobacteria contain genes for both Ni-containing (sodN) and Fe-containing (sodF) SODs. In Streptomyces coelicolor, expression of the sodF and sodN genes is inversely regulated by nickel-specific Nur, a Fur-family regulator. With sufficient nickel, Nur directly represses sodF transcription, while inducing sodN indirectly. Bioinformatic search revealed that a conserved 19-nt stretch upstream of sodN matches perfectly with the sodF downstream sequence. We found that the sodF gene produced a stable small-sized RNA species (s-SodF) of ∼90 nt that harbors the anti-sodN sequence complementary to sodN mRNA from the 5′-end up to the ribosome binding site. Absence of nearby promoters and sensitivity to 5′-phosphate-specific exonuclease indicated that the s-SodF RNA is a likely processed product of sodF mRNA. The s-SodF RNA caused a significant decrease in the half-life of the sodN mRNA. Therefore, Nur activates sodN expression through inhibiting the synthesis of sodF mRNA, from which inhibitory s-SodF RNA is generated. This reveals a novel mechanism by which antagonistic regulation of one gene is achieved by small RNA processed from the 3′UTR of another gene’s mRNA.