Entropic stabilization of the folded states of RNA due to macromolecular crowding

Biophysics Reviews
Natalia A Denesyuk, D Thirumalai

Abstract

We review the effects of macromolecular crowding on the folding of RNA by considering the simplest scenario when excluded volume interactions between crowding particles and RNA dominate. Using human telomerase enzyme as an example, we discuss how crowding can alter the equilibrium between pseudoknot and hairpin states of the same RNA molecule-a key aspect of crowder-RNA interactions. We summarize data showing that the crowding effect is significant only if the size of the spherical crowding particle is smaller than the radius of gyration of the RNA in the absence of crowding particles. The implication for function of the wild type and mutants of human telomerase is outlined by using a relationship between enzyme activity and its conformational equilibrium. In addition, we discuss the interplay between macromolecular crowding and ionic strength of the RNA buffer. Finally, we briefly review recent experiments which illustrate the connection between excluded volume due to macromolecular crowding and the thermodynamics of RNA folding.

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Citations

Dec 3, 2017·The Journal of Chemical Physics·Chwen-Yang ShewKenichi Yoshikawa
Dec 1, 2017·Biophysics Reviews·Fabio Trovato, Giordano Fumagalli
Apr 9, 2014·Expert Opinion on Investigational Drugs·Tadeusz Robak, Ewa Robak
Jun 18, 2015·Expert Opinion on Drug Discovery·Piotr Smolewski, Tadeusz Robak
Sep 23, 2014·The Journal of Chemical Physics·Wei Kang Lim, Alan R Denton
Jan 8, 2015·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Chwen-Yang Shew, Kenichi Yoshikawa
Oct 4, 2018·The Journal of Chemical Physics·Wyatt J Davis, Alan R Denton
Oct 20, 2018·Nature Communications·Wan-Jung C LaiDmitri N Ermolenko
Oct 13, 2020·Nucleic Acids Research·Fan HongPetr Šulc
Mar 4, 2021·American Journal of Physiology. Cell Physiology·Dimitrios I Zeugolis
Mar 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Naoto HoriD Thirumalai
Sep 3, 2021·The Journal of Chemical Physics·Alan R Denton, Wyatt J Davis

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