Tandem riboswitches form a natural Boolean logic gate to control purine metabolism in bacteria

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Abstract

Gene control systems sometimes interpret multiple signals to set the expression levels of the genes they regulate. In rare instances, ligand-binding riboswitch aptamers form tandem arrangements to approximate the function of specific two-input Boolean logic gates. Here we report the discovery of riboswitch aptamers for phosphoribosyl pyrophosphate (PRPP) that naturally exist either in singlet arrangements, or occur in tandem with guanine aptamers. Tandem guanine-PRPP aptamers can bind the target ligands, either independently or in combination, to approximate the function expected for an IMPLY Boolean logic gate to regulate transcription of messenger RNAs for de novo purine biosynthesis in bacteria. The existence of sophisticated all-RNA regulatory systems that sense two ancient ribonucleotide derivatives to control synthesis of RNA molecules supports the hypothesis that RNA World organisms could manage a complex metabolic state without the assistance of protein regulatory factors.

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Madeline E Sherlock

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Narasimhan Sudarsan

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Shira Stav

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Ronald R Breaker

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States

For correspondence
ronald.breaker@yale.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2165-536X

Funding

NIH Office of the Director (GM022778)

Ronald R Breaker

Howard Hughes Medical Institute (Investigator)

Ronald R Breaker

NIH Office of the Director (DE022340)

Ronald R Breaker

NIH Office of the Director (T32GM007223)

Madeline E Sherlock

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.