Refolding through a Linear Transition State Enables Fast Temperature Adaptation of a Translational Riboswitch

Biochemistry
Boris FürtigHarald Schwalbe

Abstract

The adenine-sensing riboswitch from the Gram-negative bacterium Vibrio vulnificus is an RNA-based gene regulatory element that acts in response to both its cognate low-molecular weight ligand and temperature. The combined sensitivity to environmental temperature and ligand concentration is maintained by an equilibrium of three distinct conformations involving two ligand-free states and one ligand-bound state. The key structural element that undergoes refolding in the ligand-free states comprises a 35-nucleotide temperature response module. Here, we present the structural characterization of this temperature response module. We employ high-resolution NMR spectroscopy and photocaged RNAs as molecular probes to decipher the kinetic and thermodynamic framework of the secondary structure transition in the apo state of the riboswitch. We propose a model for the transition state adopted during the thermal refolding of the temperature response module that connects two mutually exclusive long-lived and stable conformational states. This transition state is characterized by a comparatively low free activation enthalpy. A pseudoknot conformation in the transition state, as commonly seen in RNA refolding, is therefore unlikely. More likely...Continue Reading

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Citations

May 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Arthur KormanSarah A Woodson
Aug 7, 2021·Nature Communications·Vanessa de JesusBoris Fürtig

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