The TisB-IstR toxin-antitoxin system is the first known toxin-antitoxin system, induced by the SOS response in response to DNA damage. IstR sRNA 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, 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. Both genes are thought to be regulated by LexA. 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; 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 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. IstR-1 is thought to both inhibit translation of the TisB toxin, 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 degraded by RNase III. Degradation results in a +106 form, an inactive 249 nt transcript which cannot be translated; the proposed function of this toxin-antitoxin system is to cause growth arrest, rather than cell death, in response to DNA damage, allowing time for repair processes to occur. TisB translation is under LexA control, so it is induced by DNA damage as part of the SOS response. Under normal conditions little tisB mRNA is synthesised and translation is inhibited, but when DNA damage occurs tisAB is induced causing overexpression, which overrides inhibition by depleting the IstR-1 pool. Experimental data has shown effects of TisB to be decreases in transcription and replication, RNA degradation and ribosome disassembly. TisB does not affect transcription and translation directly in vitro, so these effects are thought to be downstream consequences of membrane damage. TisB insertion into the membrane is thought to result in a loss of membrane potential.
This could account for a decrease in ATP concentration in cells following triggering of the SOS response, causing slowing of cellular processes and inhibited cell growth. Toxin-antitoxin system Sib RNA hok/sok system Wagner, E. G. H.. "The toxin-antitoxin system tisB-istR1: Expression and biological role in persister phenotypes". RNA Biology. 9: 1513–1519. Doi:10.4161/rna.22578. PMID 23093802. Page for IstR at Rfam EcoCyc page for Istr-1 EcoliWiki page for TisB
Susuwahi is a census town and village in Varanasi tehsil of Varanasi district in the Indian state of Uttar Pradesh. The census town falls under the Susuwahi gram panchayat. Susuwahi Census town is about 12 kilometers South of Varanasi railway station, 320 kilometers South-East of Lucknow and 5 kilometers South-West of Banaras Hindu University main gate. Susuwahi has 1,781 families with a total population of 10,454. Sex ratio of the census town is 923 and child sex ratio is 835. Uttar Pradesh state average for both ratios is 902 respectively. Susuwahi is connected by train and by road. Nearest operational airports is Lal Bahadur Shastri Airport and nearest operational railway station is maduadih railway station. Varanasi Cantt. Varanasi district Varanasi Varanasi tehsil ^ All demographic data is based on 2011 Census of India