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NMR Structural Profiling of Transcriptional Intermediates Reveals Riboswitch Regulation by Metastable RNA Conformations

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Institute for Organic Chemisty and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe-Universität, Frankfurt/M. 60438, Germany
‡ § Department of Theoretical Chemistry and §Faculty of Computer Science, Research Group Bioinformatics and Computational Biology, University of Vienna, 1090 Vienna, Austria
Medical University of Vienna, Center for Anatomy and Cell Biology, Währingerstraße 13, 1090 Vienna, Austria
Cite this: J. Am. Chem. Soc. 2017, 139, 7, 2647–2656
Publication Date (Web):January 30, 2017
https://doi.org/10.1021/jacs.6b10429
Copyright © 2017 American Chemical Society
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Abstract

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Gene repression induced by the formation of transcriptional terminators represents a prime example for the coupling of RNA synthesis, folding, and regulation. In this context, mapping the changes in available conformational space of transcription intermediates during RNA synthesis is important to understand riboswitch function. A majority of riboswitches, an important class of small metabolite-sensing regulatory RNAs, act as transcriptional regulators, but the dependence of ligand binding and the subsequent allosteric conformational switch on mRNA transcript length has not yet been investigated. We show a strict fine-tuning of binding and sequence-dependent alterations of conformational space by structural analysis of all relevant transcription intermediates at single-nucleotide resolution for the I-A type 2′dG-sensing riboswitch from Mesoplasma florum by NMR spectroscopy. Our results provide a general framework to dissect the coupling of synthesis and folding essential for riboswitch function, revealing the importance of metastable states for RNA-based gene regulation.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.6b10429.

  • NMR characterization of the antiterminator conformation, detailed secondary structure screening of transcriptional intermediates, effect of Mg2+ on the antiterminator conformation, simulations of cotranscriptional folding, transcription assays, and ITC data of transcriptional intermediates (PDF)

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This article is cited by 28 publications.

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