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An anionic ligand snap-locks a long-range interaction in a magnesium-folded riboswitch
Rajeev Yadav1,2, Julia R Widom1,3, Adrien Chauvier1
1Single Molecule Analysis Group, Department of Chemistry and Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Nature Communications
|January 12, 2022
Summary
Fluoride riboswitches control gene expression. This study reveals how fluoride and magnesium ions stabilize RNA structures, enabling cellular detoxification.
Area of Science:
- Molecular Biology
- RNA Biology
- Biochemistry
Background:
- The crcB riboswitch in Bacillus cereus regulates gene expression in response to fluoride.
- Riboswitches are non-coding RNA elements with crucial regulatory functions.
Purpose of the Study:
- To investigate the dynamic conformations of the crcB fluoride riboswitch during transcription.
- To elucidate the molecular mechanisms of fluoride-induced riboswitch activation.
Main Methods:
- Single-molecule Förster Resonance Energy Transfer (smFRET) to observe RNA dynamics.
- Analysis of RNA polymerase-RNA interactions.
Main Results:
- Identified three interconverting conformations: two undocked and one docked pseudoknotted state.
- Fluoride ions specifically stabilize the magnesium-bound docked state.
- A single base pair (A40-U48) is critical for docking, not the pseudoknot.
Conclusions:
- Fluoride binding, in cooperation with magnesium, drives riboswitch docking.
- RNA polymerase pausing influences riboswitch conformational selection.
- Early fluoride binding facilitates the transition to the functional docked state for gene regulation.
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