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The discovery of numerous riboswitch classes reveals that many of these RNA structures regulate gene expression in response to the selective binding of coenzymes and signaling molecules derived from RNA monomers or their precursors. It has been proposed that many coenzymes might be of ancient origin, based on their universal distribution in biology and their RNA-like chemical composition. In this Review, which includes four figures and 103 references, we discuss the findings that support the hypothesis that common RNA-derived signaling compounds are ancient and speculate on the possible complexity of the chemical language that might have been used by life-forms long before proteins emerged.

Abstract

The possibility of an RNA World is based on the notion that life on Earth passed through a primitive phase without proteins, a time when all genomes and enzymes were composed of ribonucleic acids. Numerous apparent vestiges of this ancient RNA World remain today, including many nucleotide-derived coenzymes, self-processing ribozymes, metabolite-binding riboswitches, and even ribosomes. Many of the most common signaling molecules and second messengers used by modern organisms are also formed from RNA nucleotides or their precursors. For example, nucleotide derivatives such as cAMP, ppGpp, and ZTP, as well as the cyclic dinucleotides c-di-GMP and c-di-AMP, are intimately involved in signaling diverse physiological or metabolic changes in bacteria and other organisms. We describe the potential diversity of this "lost language" of the RNA World and speculate on whether additional components of this ancient communication machinery might remain hidden though still very much relevant to modern cells.
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Science Signaling
Volume 10 | Issue 483
June 2017

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Received: 30 January 2017
Accepted: 9 May 2017

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Acknowledgments

We thank A. Roth, N. Sudarsan, and M. Sherlock for helpful discussions and comments on the manuscript. Funding: This work was supported by NIH grant GM022778 to R.R.B., whose research on RNA is also supported by the Howard Hughes Medical Institute. Author contributions: Both authors contributed to writing this manuscript and generating figures. Competing interests: The authors declare that they have no competing interests.

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Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
Present address: Howard Hughes Medical Institute and Department of Chemistry and Chemical Biology, Harvard University, 13 Oxford Street, Cambridge, MA 02138, USA.
Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
Department of Molecular Biophysics and Biochemistry, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.

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National Institutes of Health: award299872, GM022778

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†Corresponding author. Email: [email protected]

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