The lost language of the RNA World

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Science Signaling  13 Jun 2017:
Vol. 10, Issue 483, eaam8812
DOI: 10.1126/scisignal.aam8812


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.


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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