Cotranscriptional RNA strand exchange underlies the gene regulation mechanism in a purine-sensing transcriptional riboswitch

Luyi Cheng, Elise N White, Naomi L Brandt, Angela M Yu, Alan A Chen, Julius B Lucks

Nucleic Acids Research, gkac102, https://doi.org/10.1093/nar/gkac102

Riboswitches have challenged our understanding of biological regulation for almost two decades. The ability of small molecules to bind to RNA and control gene expression offers another layer of regulation and the potential for direct action by compounds in the environment. While some riboswitches have been well studied, we lack a general understanding of how changes in RNA structure switch genetic expression from “On” to “Off”. In this study, the authors propose an elegant “strand displacement” model to explain how the RNA structure shifts between “On” and “Off” states as the concentration of small molecule ligand changes. These observations help us to understand how riboswitches enable genetic decision-making. The data provide a possible general mechanism for understanding how the competition between different strand displacement outcomes can influence RNA folding. Understanding RNA folding pathways could advance the successful design of drugs that target RNA.

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