The TisB-IstR toxin-antitoxin system is the first known toxin-antitoxin system which is induced by the SOS response in response to DNA damage. IstR-1 and IstR-2 IstR sRNA (inhibitor of SOS-induced toxicity by RNA) is a family of non-coding RNA first identified in Escherichia coli. There are two small RNAs encoded by the IstR locus: IstR-1 and IstR-2, of which IstR-1 works as antitoxins against the toxic protein TisB (toxicity-induced by SOS B) which is encoded by the neighbouring tisAB gene. IstR-1 is a 75 nucleotide transcript expressed constitutively throughout growth, whereas IstR-2 is a 140 nucleotide transcript induced by Mitomycin C (MMC). Both IstR-2 and tisAB are thought to be regulated by LexA while IstR-1 is constitutively transcribed. Deletion analysis confirmed the function of IstR, E. coli strain K-12 could not grow in the absence of IstR when tisAB was present. Inserting IstR genes on a plasmid allowed the bacteria to grow normally. Further studies showed that expression of IstR-1 alone is enough to remedy the toxic effects of TisB. IstR-2 is not involved in the regulation of tisAB. TisAB The tisAB locus codes for two genes: tisA and tisB. The tisA reading frame was shown through a translation assay to not be translated. Its sequence is unconserved across species. TisB is a 29 amino acid peptide widely conserved in enterobacteria. TisB is responsible for conferring toxicity through suspected membrane disruption. Upon translation of the tisB gene, a +1 inactive primary transcript mRNA is produced, which must be endonucleolytically processed 42 nucleotides from the 5' end to yield a +42 translationally competent mRNA. In the +42 form, the mRNA has a ribosome loading/standby site in an unstructured region >80 nt upstream of the tisB ribosome binding site, thus allowing translation of the TisB protein. This standby site is structurally unavailable in the inactive forms of the tisB mRNA (the +1 form and the +106 form produced by RNase III cleavage). Mechanism of TisB inhibition by IstR-1 IstR-1 is thought to both inhibit translation of the TisB toxin, and promote RNase III cleavage of the RNA duplex formed when IstR-1 base pairs to tisB mRNA. Binding of the complementary sequence of istR-1 sRNA to tisB mRNA in the ribosome standby site is thought to prevent loading of ribosomes and therefore prevent translation of the TisB protein. A RACE analysis confirmed that IstR-1 binds TisB mRNA and the duplex is then degraded