» Articles » PMID: 30328748

Kinetics Coming into Focus: Single-molecule Microscopy of Riboswitch Dynamics

Overview
Journal RNA Biol
Specialty Molecular Biology
Date 2018 Oct 18
PMID 30328748
Citations 24
Authors
Affiliations
Soon will be listed here.
Abstract

Riboswitches are dynamic RNA motifs that are mostly embedded in the 5'-untranslated regions of bacterial mRNAs, where they regulate gene expression transcriptionally or translationally by undergoing conformational changes upon binding of a small metabolite or ion. Due to the small size of typical ligands, relatively little free energy is available from ligand binding to overcome the often high energetic barrier of reshaping RNA structure. Instead, most riboswitches appear to take advantage of the directional and hierarchical folding of RNA by employing the ligand as a structural 'linchpin' to adjust the kinetic partitioning between alternate folds. In this model, even small, local structural and kinetic effects of ligand binding can cascade into global RNA conformational changes affecting gene expression. Single-molecule (SM) microscopy tools are uniquely suited to study such kinetically controlled RNA folding since they avoid the ensemble averaging of bulk techniques that loses sight of unsynchronized, transient, and/or multi-state kinetic behavior. This review summarizes how SM methods have begun to unravel riboswitch-mediated gene regulation.

Citing Articles

Determining structures of RNA conformers using AFM and deep neural networks.

Degenhardt M, Degenhardt H, Bhandari Y, Lee Y, Ding J, Yu P Nature. 2024; 637(8048):1234-1243.

PMID: 39695231 PMC: 11779638. DOI: 10.1038/s41586-024-07559-x.


The conformational space of RNase P RNA in solution.

Lee Y, Degenhardt M, Skeparnias I, Degenhardt H, Bhandari Y, Yu P Nature. 2024; 637(8048):1244-1251.

PMID: 39695229 PMC: 11779636. DOI: 10.1038/s41586-024-08336-6.


NusG-dependent RNA polymerase pausing is a common feature of riboswitch regulatory mechanisms.

Jayasinghe O, Ritchey L, Breil T, Newman P, Yakhnin H, Babitzke P Nucleic Acids Res. 2024; 52(21):12945-12960.

PMID: 39494516 PMC: 11602163. DOI: 10.1093/nar/gkae981.


Opportunities for Riboswitch Inhibition by Targeting Co-Transcriptional RNA Folding Events.

Stephen C, Palmer D, Mishanina T Int J Mol Sci. 2024; 25(19).

PMID: 39408823 PMC: 11476745. DOI: 10.3390/ijms251910495.


Mechanistic analysis of Riboswitch Ligand interactions provides insights into pharmacological control over gene expression.

Parmar S, Bume D, Connelly C, Boer R, Prestwood P, Wang Z Nat Commun. 2024; 15(1):8173.

PMID: 39289353 PMC: 11408619. DOI: 10.1038/s41467-024-52235-3.


References
1.
Widom J, Nedialkov Y, Rai V, Hayes R, Brooks 3rd C, Artsimovitch I . Ligand Modulates Cross-Coupling between Riboswitch Folding and Transcriptional Pausing. Mol Cell. 2018; 72(3):541-552.e6. PMC: 6565381. DOI: 10.1016/j.molcel.2018.08.046. View

2.
Fallmann J, Will S, Engelhardt J, Gruning B, Backofen R, Stadler P . Recent advances in RNA folding. J Biotechnol. 2017; 261:97-104. DOI: 10.1016/j.jbiotec.2017.07.007. View

3.
Feng J, Walter N, Brooks 3rd C . Cooperative and directional folding of the preQ1 riboswitch aptamer domain. J Am Chem Soc. 2011; 133(12):4196-9. PMC: 3109358. DOI: 10.1021/ja110411m. View

4.
Barrick J, Corbino K, Winkler W, Nahvi A, Mandal M, Collins J . New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc Natl Acad Sci U S A. 2004; 101(17):6421-6. PMC: 404060. DOI: 10.1073/pnas.0308014101. View

5.
Walter N, Huang C, Manzo A, Sobhy M . Do-it-yourself guide: how to use the modern single-molecule toolkit. Nat Methods. 2008; 5(6):475-89. PMC: 2574008. DOI: 10.1038/nmeth.1215. View