1. A small RNA that cooperatively senses two stacked metabolites in one pocket for gene control.
- Author
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Schroeder GM, Cavender CE, Blau ME, Jenkins JL, Mathews DH, and Wedekind JE
- Subjects
- Base Pairing, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli genetics, Escherichia coli metabolism, Gene Expression, Gene Expression Regulation, Bacterial, Genetic Vectors chemistry, Genetic Vectors metabolism, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Neisseria gonorrhoeae metabolism, Nucleic Acid Conformation, Nucleoside Q biosynthesis, Pyrimidinones metabolism, Pyrroles metabolism, RNA, Bacterial genetics, RNA, Bacterial metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Neisseria gonorrhoeae genetics, Nucleoside Q chemistry, Pyrimidinones chemistry, Pyrroles chemistry, RNA, Bacterial chemistry, RNA, Messenger chemistry, Riboswitch
- 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 preQ
1 -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., (© 2022. The Author(s).)- Published
- 2022
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