Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 23, Pages 6052-6057Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1720406115
Keywords
branched chain amino acid; guanosine tetraphosphate; logic gate; stringent response; ykkC motif RNA
Categories
Funding
- NIH [GM022778, DE022340]
- NIH Cellular and Molecular Biology Training Grant [T32GM007223]
- Howard Hughes Medical Institute
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Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch classes first emerged during the RNA World, which is proposed to have existed before proteins were present. Here we report the discovery and biochemical validation of a natural riboswitch class that selectively binds guanosine tetraphosphate ( ppGpp), a widespread signaling molecule and bacterial alarmone derived from the ribonucleotide GTP. Riboswitches for ppGpp are predicted to regulate genes involved in branched-chain amino acid biosynthesis and transport, as well as other gene classes that previously had not been implicated to be part of its signaling network. This newfound riboswitch-alarmone partnership supports the hypothesis that prominent RNA World signaling pathways have been retained by modern cells to control key biological processes.
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