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  • 1
    Publication Date: 2016-04-28
    Description: Riboswitches and attenuators are cis-regulatory RNA elements, most of which control bacterial gene expression via metabolite-mediated, premature transcription termination. We developed an unbiased experimental approach for genome-wide discovery of such ribo-regulators in bacteria. We also devised an experimental platform that quantitatively measures the in vivo activity of all such regulators in parallel and enables rapid screening for ribo-regulators that respond to metabolites of choice. Using this approach, we detected numerous antibiotic-responsive ribo-regulators that control antibiotic resistance genes in pathogens and in the human microbiome. Studying one such regulator in Listeria monocytogenes revealed an attenuation mechanism mediated by antibiotic-stalled ribosomes. Our results expose broad roles for conditional termination in regulating antibiotic resistance and provide a tool for discovering riboswitches and attenuators that respond to previously unknown ligands.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dar, Daniel -- Shamir, Maya -- Mellin, J R -- Koutero, Mikael -- Stern-Ginossar, Noam -- Cossart, Pascale -- Sorek, Rotem -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):aad9822. doi: 10.1126/science.aad9822.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Institut Pasteur, Unite des Interactions Bacteries-Cellules, Paris, F-75015 France. INSERM, U604, Paris, F-75015 France. Institut National de la Recherche Agronomique, USC2020, Paris, F-75015 France. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Enterococcus faecalis/drug effects ; Gastrointestinal Microbiome/drug effects/genetics ; *Gene Expression Regulation, Bacterial ; Genome, Bacterial/genetics ; Genome-Wide Association Study/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Listeria monocytogenes/drug effects/genetics ; Ribosomes/metabolism ; Riboswitch/*genetics ; Sequence Analysis, RNA/methods ; *Transcription Termination, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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