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Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+)
Riboswitches are cis-acting regulatory RNA biosensors that rival the efficiency of those found in proteins. At the heart of their regulatory function is the formation of a highly specific aptamer–ligand complex. Understanding how these RNAs recognize the ligand to regulate gene expression at physiol...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614840/ https://www.ncbi.nlm.nih.gov/pubmed/31045204 http://dx.doi.org/10.1093/nar/gkz316 |
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author | McCluskey, Kaley Boudreault, Julien St-Pierre, Patrick Perez-Gonzalez, Cibran Chauvier, Adrien Rizzi, Adrien Beauregard, Pascale B Lafontaine, Daniel A Penedo, J Carlos |
author_facet | McCluskey, Kaley Boudreault, Julien St-Pierre, Patrick Perez-Gonzalez, Cibran Chauvier, Adrien Rizzi, Adrien Beauregard, Pascale B Lafontaine, Daniel A Penedo, J Carlos |
author_sort | McCluskey, Kaley |
collection | PubMed |
description | Riboswitches are cis-acting regulatory RNA biosensors that rival the efficiency of those found in proteins. At the heart of their regulatory function is the formation of a highly specific aptamer–ligand complex. Understanding how these RNAs recognize the ligand to regulate gene expression at physiological concentrations of Mg(2+) ions and ligand is critical given their broad impact on bacterial gene expression and their potential as antibiotic targets. In this work, we used single-molecule FRET and biochemical techniques to demonstrate that Mg(2+) ions act as fine-tuning elements of the amino acid-sensing lysC aptamer's ligand-free structure in the mesophile Bacillus subtilis. Mg(2+) interactions with the aptamer produce encounter complexes with strikingly different sensitivities to the ligand in different, yet equally accessible, physiological ionic conditions. Our results demonstrate that the aptamer adapts its structure and folding landscape on a Mg(2+)-tunable scale to efficiently respond to changes in intracellular lysine of more than two orders of magnitude. The remarkable tunability of the lysC aptamer by sub-millimolar variations in the physiological concentration of Mg(2+) ions suggests that some single-aptamer riboswitches have exploited the coupling of cellular levels of ligand and divalent metal ions to tightly control gene expression. |
format | Online Article Text |
id | pubmed-6614840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-66148402019-07-12 Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) McCluskey, Kaley Boudreault, Julien St-Pierre, Patrick Perez-Gonzalez, Cibran Chauvier, Adrien Rizzi, Adrien Beauregard, Pascale B Lafontaine, Daniel A Penedo, J Carlos Nucleic Acids Res RNA and RNA-protein complexes Riboswitches are cis-acting regulatory RNA biosensors that rival the efficiency of those found in proteins. At the heart of their regulatory function is the formation of a highly specific aptamer–ligand complex. Understanding how these RNAs recognize the ligand to regulate gene expression at physiological concentrations of Mg(2+) ions and ligand is critical given their broad impact on bacterial gene expression and their potential as antibiotic targets. In this work, we used single-molecule FRET and biochemical techniques to demonstrate that Mg(2+) ions act as fine-tuning elements of the amino acid-sensing lysC aptamer's ligand-free structure in the mesophile Bacillus subtilis. Mg(2+) interactions with the aptamer produce encounter complexes with strikingly different sensitivities to the ligand in different, yet equally accessible, physiological ionic conditions. Our results demonstrate that the aptamer adapts its structure and folding landscape on a Mg(2+)-tunable scale to efficiently respond to changes in intracellular lysine of more than two orders of magnitude. The remarkable tunability of the lysC aptamer by sub-millimolar variations in the physiological concentration of Mg(2+) ions suggests that some single-aptamer riboswitches have exploited the coupling of cellular levels of ligand and divalent metal ions to tightly control gene expression. Oxford University Press 2019-07-09 2019-05-02 /pmc/articles/PMC6614840/ /pubmed/31045204 http://dx.doi.org/10.1093/nar/gkz316 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RNA and RNA-protein complexes McCluskey, Kaley Boudreault, Julien St-Pierre, Patrick Perez-Gonzalez, Cibran Chauvier, Adrien Rizzi, Adrien Beauregard, Pascale B Lafontaine, Daniel A Penedo, J Carlos Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title | Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title_full | Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title_fullStr | Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title_full_unstemmed | Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title_short | Unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological Mg(2+) |
title_sort | unprecedented tunability of riboswitch structure and regulatory function by sub-millimolar variations in physiological mg(2+) |
topic | RNA and RNA-protein complexes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614840/ https://www.ncbi.nlm.nih.gov/pubmed/31045204 http://dx.doi.org/10.1093/nar/gkz316 |
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