Single-molecule Studies of Riboswitch Folding

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2014 Apr 15

PMID 24727093

Citations 32

Authors

Andrew Savinov

Christian F Perez

Steven M Block

Affiliations

Soon will be listed here.

Abstract

The folding dynamics of riboswitches are central to their ability to modulate gene expression in response to environmental cues. In most cases, a structural competition between the formation of a ligand-binding aptamer and an expression platform (or some other competing off-state) determines the regulatory outcome. Here, we review single-molecule studies of riboswitch folding and function, predominantly carried out using single-molecule FRET or optical trapping approaches. Recent results have supplied new insights into riboswitch folding energy landscapes, the mechanisms of ligand binding, the roles played by divalent ions, the applicability of hierarchical folding models, and kinetic vs. thermodynamic control schemes. We anticipate that future work, based on improved data sets and potentially combining multiple experimental techniques, will enable the development of more complete models for complex RNA folding processes. This article is part of a Special Issue entitled: Riboswitches.

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References

Kim J, Breaker R . Purine sensing by riboswitches. Biol Cell. 2007; 100(1):1-11. DOI: 10.1042/BC20070088. View

Cheah M, Wachter A, Sudarsan N, Breaker R . Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature. 2007; 447(7143):497-500. DOI: 10.1038/nature05769. View

Garst A, Heroux A, Rambo R, Batey R . Crystal structure of the lysine riboswitch regulatory mRNA element. J Biol Chem. 2008; 283(33):22347-51. PMC: 2504901. DOI: 10.1074/jbc.C800120200. View

Blanco M, Walter N . Analysis of complex single-molecule FRET time trajectories. Methods Enzymol. 2010; 472:153-78. PMC: 3012381. DOI: 10.1016/S0076-6879(10)72011-5. View

Neupane K, Yu H, Foster D, Wang F, Woodside M . Single-molecule force spectroscopy of the add adenine riboswitch relates folding to regulatory mechanism. Nucleic Acids Res. 2011; 39(17):7677-87. PMC: 3177178. DOI: 10.1093/nar/gkr305. View

Tinoco Jr I, Bustamante C . How RNA folds. J Mol Biol. 1999; 293(2):271-81. DOI: 10.1006/jmbi.1999.3001. View

Smith K, Lipchock S, Livingston A, Shanahan C, Strobel S . Structural and biochemical determinants of ligand binding by the c-di-GMP riboswitch . Biochemistry. 2010; 49(34):7351-9. PMC: 3146058. DOI: 10.1021/bi100671e. View

Zhou R, Schlierf M, Ha T . Force-fluorescence spectroscopy at the single-molecule level. Methods Enzymol. 2010; 475:405-26. DOI: 10.1016/S0076-6879(10)75016-3. View

Lang M, Asbury C, Shaevitz J, Block S . An automated two-dimensional optical force clamp for single molecule studies. Biophys J. 2002; 83(1):491-501. PMC: 1302163. DOI: 10.1016/S0006-3495(02)75185-0. View

10.

Sudarsan N, Cohen-Chalamish S, Nakamura S, Emilsson G, Breaker R . Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem Biol. 2005; 12(12):1325-35. DOI: 10.1016/j.chembiol.2005.10.007. View

11.

Dalgarno P, Bordello J, Morris R, St-Pierre P, Dube A, Samuel I . Single-molecule chemical denaturation of riboswitches. Nucleic Acids Res. 2013; 41(7):4253-65. PMC: 3627600. DOI: 10.1093/nar/gkt128. View

12.

Pereira M, Nikolova E, Hiley S, Jaikaran D, Collins R, Walter N . Single VS ribozyme molecules reveal dynamic and hierarchical folding toward catalysis. J Mol Biol. 2008; 382(2):496-509. PMC: 2575853. DOI: 10.1016/j.jmb.2008.07.020. View

13.

Misra V, Draper D . The interpretation of Mg(2+) binding isotherms for nucleic acids using Poisson-Boltzmann theory. J Mol Biol. 1999; 294(5):1135-47. DOI: 10.1006/jmbi.1999.3334. View

14.

Misra V, Shiman R, Draper D . A thermodynamic framework for the magnesium-dependent folding of RNA. Biopolymers. 2003; 69(1):118-36. DOI: 10.1002/bip.10353. View

15.

Solomatin S, Greenfeld M, Chu S, Herschlag D . Multiple native states reveal persistent ruggedness of an RNA folding landscape. Nature. 2010; 463(7281):681-4. PMC: 2818749. DOI: 10.1038/nature08717. View

16.

Souliere M, Altman R, Schwarz V, Haller A, Blanchard S, Micura R . Tuning a riboswitch response through structural extension of a pseudoknot. Proc Natl Acad Sci U S A. 2013; 110(35):E3256-64. PMC: 3761628. DOI: 10.1073/pnas.1304585110. View

17.

Svoboda K, Block S . Biological applications of optical forces. Annu Rev Biophys Biomol Struct. 1994; 23:247-85. DOI: 10.1146/annurev.bb.23.060194.001335. View

18.

Rieder R, Lang K, Graber D, Micura R . Ligand-induced folding of the adenosine deaminase A-riboswitch and implications on riboswitch translational control. Chembiochem. 2007; 8(8):896-902. DOI: 10.1002/cbic.200700057. View

19.

Altman R, Terry D, Zhou Z, Zheng Q, Geggier P, Kolster R . Cyanine fluorophore derivatives with enhanced photostability. Nat Methods. 2011; 9(1):68-71. PMC: 3433158. DOI: 10.1038/nmeth.1774. View

20.

Hohng S, Joo C, Ha T . Single-molecule three-color FRET. Biophys J. 2004; 87(2):1328-37. PMC: 1304471. DOI: 10.1529/biophysj.104.043935. View