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A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control

Griffin M. Schroeder, Chapin E. Cavender, Maya E. Blau, Jermaine L. Jenkins, David H. Mathews and Joseph E. Wedekind ()
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Griffin M. Schroeder: University of Rochester School of Medicine & Dentistry
Chapin E. Cavender: University of Rochester School of Medicine & Dentistry
Maya E. Blau: University of Rochester
Jermaine L. Jenkins: University of Rochester School of Medicine & Dentistry
David H. Mathews: University of Rochester School of Medicine & Dentistry
Joseph E. Wedekind: University of Rochester School of Medicine & Dentistry

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: Abstract Riboswitches are structured non-coding RNAs often located upstream of essential genes in bacterial messenger RNAs. Such RNAs regulate expression of downstream genes by recognizing a specific cellular effector. Although nearly 50 riboswitch classes are known, only a handful recognize multiple effectors. Here, we report the 2.60-Å resolution co-crystal structure of a class I type I preQ1-sensing riboswitch that reveals two effectors stacked atop one another in a single binding pocket. These effectors bind with positive cooperativity in vitro and both molecules are necessary for gene regulation in bacterial cells. Stacked effector recognition appears to be a hallmark of the largest subgroup of preQ1 riboswitches, including those from pathogens such as Neisseria gonorrhoeae. We postulate that binding to stacked effectors arose in the RNA World to closely position two substrates for RNA-mediated catalysis. These findings expand known effector recognition capabilities of riboswitches and have implications for antimicrobial development.

Date: 2022
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DOI: 10.1038/s41467-021-27790-8

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