Entropy Driving the Mg²⁺-Induced Folding of TPP Riboswitch RNA

Abstract

Mg 2+ is well known to facilitate the structural folding of RNA. However, the thermodynamic and dynamic roles of Mg 2+ in RNA folding remain elusive. Here, we exploit singlemolecule fluorescence resonance energy transfer (smFRET) and isothermal titration calorimetry (ITC) to study the mechanism of Mg 2+ in facilitating the folding of thiamine pyrophosphate (TPP) riboswitch RNA. The results of smFRET identify that the presence of Mg 2+ compacts the RNA and enlarges the conformational dispersity among individual RNA molecules, resulting in a large gain of entropy. The compact yet flexible conformations triggered by Mg 2+ may help the riboswitch recognize its specific ligand and further fold. This is supported by the ITC experiments, in which the Mg 2+ -induced RNA folding is driven by entropy (ΔS) instead of enthalpy (ΔH). Our results complement the understanding of the Mg 2+ -induced RNA folding. The strategy developed in this work can be used to model other RNAs' folding under different conditions.

Mn2+-induced structural flexibility enhances the entire catalytic cycle and the cleavage of mismatches in prokaryotic argonaute proteins

“…Divalent cations play a fundamental role in biomacromolecule dynamics, primarily situated in ribosomes, 50,51 enzymes, 30,52,53 and structural proteins. 54 The proper function and stability of such proteins necessitate the presence of ions.…”

Targeting FMN, TPP, SAM-I, and glmS Riboswitches with Chimeric Antisense Oligonucleotides for Completely Rational Antibacterial Drug Development

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