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Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli
Short regulatory RNAs are widespread in bacteria, and many function through antisense recognition of mRNA. Among the best studied antisense transcripts are RNA antitoxins that repress toxin mRNA translation. The hok/sok locus of plasmid R1 from Escherichia coli is an established model for RNA antito...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635323/ https://www.ncbi.nlm.nih.gov/pubmed/17065468 http://dx.doi.org/10.1093/nar/gkl750 |
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author | Faridani, Omid R. Nikravesh, Abbas Pandey, Deo Prakash Gerdes, Kenn Good, Liam |
author_facet | Faridani, Omid R. Nikravesh, Abbas Pandey, Deo Prakash Gerdes, Kenn Good, Liam |
author_sort | Faridani, Omid R. |
collection | PubMed |
description | Short regulatory RNAs are widespread in bacteria, and many function through antisense recognition of mRNA. Among the best studied antisense transcripts are RNA antitoxins that repress toxin mRNA translation. The hok/sok locus of plasmid R1 from Escherichia coli is an established model for RNA antitoxin action. Base-pairing between hok mRNA and Sok-antisense-RNA increases plasmid maintenance through post-segregational-killing of plasmid-free progeny cells. To test the model and the idea that sequestration of Sok-RNA activity could provide a novel antimicrobial strategy, we designed anti Sok peptide nucleic acid (PNA) oligomers that, according to the model, would act as competitive inhibitors of hok mRNA::Sok-RNA interactions. In hok/sok-carrying cells, anti Sok PNAs were more bactericidal than rifampicin. Also, anti Sok PNAs induced ghost cell morphology and an accumulation of mature hok mRNA, consistent with cell killing through synthesis of Hok protein. The results support the sense/antisense model for hok mRNA repression by Sok-RNA and demonstrate that antisense agents can be used to out-compete RNA::RNA interactions in bacteria. Finally, BLAST analyses of ≈200 prokaryotic genomes revealed that many enteric bacteria have multiple hok/sok homologous and analogous RNA-regulated toxin–antitoxin loci. Therefore, it is possible to activate suicide in bacteria by targeting antitoxins. |
format | Text |
id | pubmed-1635323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-16353232006-12-26 Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli Faridani, Omid R. Nikravesh, Abbas Pandey, Deo Prakash Gerdes, Kenn Good, Liam Nucleic Acids Res RNA Short regulatory RNAs are widespread in bacteria, and many function through antisense recognition of mRNA. Among the best studied antisense transcripts are RNA antitoxins that repress toxin mRNA translation. The hok/sok locus of plasmid R1 from Escherichia coli is an established model for RNA antitoxin action. Base-pairing between hok mRNA and Sok-antisense-RNA increases plasmid maintenance through post-segregational-killing of plasmid-free progeny cells. To test the model and the idea that sequestration of Sok-RNA activity could provide a novel antimicrobial strategy, we designed anti Sok peptide nucleic acid (PNA) oligomers that, according to the model, would act as competitive inhibitors of hok mRNA::Sok-RNA interactions. In hok/sok-carrying cells, anti Sok PNAs were more bactericidal than rifampicin. Also, anti Sok PNAs induced ghost cell morphology and an accumulation of mature hok mRNA, consistent with cell killing through synthesis of Hok protein. The results support the sense/antisense model for hok mRNA repression by Sok-RNA and demonstrate that antisense agents can be used to out-compete RNA::RNA interactions in bacteria. Finally, BLAST analyses of ≈200 prokaryotic genomes revealed that many enteric bacteria have multiple hok/sok homologous and analogous RNA-regulated toxin–antitoxin loci. Therefore, it is possible to activate suicide in bacteria by targeting antitoxins. Oxford University Press 2006-11 2006-10-25 /pmc/articles/PMC1635323/ /pubmed/17065468 http://dx.doi.org/10.1093/nar/gkl750 Text en © 2006 The Author(s) |
spellingShingle | RNA Faridani, Omid R. Nikravesh, Abbas Pandey, Deo Prakash Gerdes, Kenn Good, Liam Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title | Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title_full | Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title_fullStr | Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title_full_unstemmed | Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title_short | Competitive inhibition of natural antisense Sok-RNA interactions activates Hok-mediated cell killing in Escherichia coli |
title_sort | competitive inhibition of natural antisense sok-rna interactions activates hok-mediated cell killing in escherichia coli |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1635323/ https://www.ncbi.nlm.nih.gov/pubmed/17065468 http://dx.doi.org/10.1093/nar/gkl750 |
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