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Proc Natl Acad Sci U S A. 2018 Jun 5;115(23):6052-6057. doi: 10.1073/pnas.1720406115. Epub 2018 May 21.

Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.

Author information

1
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8103.
2
Howard Hughes Medical Institute, Yale University, New Haven, CT 06520-8103.
3
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520-8103; ronald.breaker@yale.edu.
4
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103.

Abstract

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.

KEYWORDS:

branched chain amino acid; guanosine tetraphosphate; logic gate; stringent response; ykkC motif RNA

PMID:
29784782
PMCID:
PMC6003355
DOI:
10.1073/pnas.1720406115
[Indexed for MEDLINE]
Free PMC Article

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