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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...

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Autores principales: McCluskey, Kaley, Boudreault, Julien, St-Pierre, Patrick, Perez-Gonzalez, Cibran, Chauvier, Adrien, Rizzi, Adrien, Beauregard, Pascale B, Lafontaine, Daniel A, Penedo, J Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
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.
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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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