A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics
Expression of many bacterial genes is regulated by cis- and trans-acting elements in their 5’ upstream regions (URs). Cis-acting regulatory elements in URs include upstream ORFs (uORFs), short ORFs that sense translation stress that manifests as ribosomes stalling at specific codons within the uORF....
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/101217 |
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| author | Gabriele Baniulyte Joseph T Wade |
| author_facet | Gabriele Baniulyte Joseph T Wade |
| author_sort | Gabriele Baniulyte |
| collection | DOAJ |
| description | Expression of many bacterial genes is regulated by cis- and trans-acting elements in their 5’ upstream regions (URs). Cis-acting regulatory elements in URs include upstream ORFs (uORFs), short ORFs that sense translation stress that manifests as ribosomes stalling at specific codons within the uORF. Here, we show that the transcript encoding the Escherichia coli TopAI-YjhQ toxin–antitoxin system is regulated by a uORF that we name ‘toiL’. We propose that in the absence of translation stress, a secondary structure in the UR represses translation of the topAI transcript by occluding the ribosome-binding site. Translation repression of topAI leads to premature Rho-dependent transcription termination within the topAI ORF. At least five different classes of ribosome-targeting antibiotics relieve repression of topAI. Our data suggest that these antibiotics function by stalling ribosomes at different positions within toiL, thereby altering the RNA secondary structure around the topAI ribosome-binding site. Thus, toiL is a multipurpose uORF that can respond to a wide variety of translation stresses. |
| format | Article |
| id | doaj-art-e5af5bb729814b0a97f525c3b8ae38dc |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-e5af5bb729814b0a97f525c3b8ae38dc2025-08-20T02:34:24ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011310.7554/eLife.101217A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibioticsGabriele Baniulyte0https://orcid.org/0000-0003-0235-7938Joseph T Wade1https://orcid.org/0000-0002-9779-3160Department of Biomedical Sciences, School of Public Health, University at Albany, SUNY, Rensselaer, United StatesDepartment of Biomedical Sciences, School of Public Health, University at Albany, SUNY, Rensselaer, United States; Wadsworth Center, New York State Department of Health, Albany, United States; RNA Institute, University at Albany, SUNY, Albany, United StatesExpression of many bacterial genes is regulated by cis- and trans-acting elements in their 5’ upstream regions (URs). Cis-acting regulatory elements in URs include upstream ORFs (uORFs), short ORFs that sense translation stress that manifests as ribosomes stalling at specific codons within the uORF. Here, we show that the transcript encoding the Escherichia coli TopAI-YjhQ toxin–antitoxin system is regulated by a uORF that we name ‘toiL’. We propose that in the absence of translation stress, a secondary structure in the UR represses translation of the topAI transcript by occluding the ribosome-binding site. Translation repression of topAI leads to premature Rho-dependent transcription termination within the topAI ORF. At least five different classes of ribosome-targeting antibiotics relieve repression of topAI. Our data suggest that these antibiotics function by stalling ribosomes at different positions within toiL, thereby altering the RNA secondary structure around the topAI ribosome-binding site. Thus, toiL is a multipurpose uORF that can respond to a wide variety of translation stresses.https://elifesciences.org/articles/101217uORFtranslationRho-dependent transcription terminationribosome |
| spellingShingle | Gabriele Baniulyte Joseph T Wade A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics eLife uORF translation Rho-dependent transcription termination ribosome |
| title | A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics |
| title_full | A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics |
| title_fullStr | A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics |
| title_full_unstemmed | A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics |
| title_short | A bacterial regulatory uORF senses multiple classes of ribosome-targeting antibiotics |
| title_sort | bacterial regulatory uorf senses multiple classes of ribosome targeting antibiotics |
| topic | uORF translation Rho-dependent transcription termination ribosome |
| url | https://elifesciences.org/articles/101217 |
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