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The glmS riboswitch integrates signals from activating and inhibitory metabolites in vivo

Nature Structural & Molecular Biology volume 18, pages 359–363 (2011)Cite this article

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Abstract

The glmS riboswitch belongs to the family of regulatory RNAs that provide feedback regulation of metabolic genes. It is also a ribozyme that self-cleaves upon binding glucosamine-6-phosphate, the product of the enzyme encoded by glmS. The ligand concentration dependence of intracellular self-cleavage kinetics was measured for the first time in a yeast model system and unexpectedly revealed that this riboswitch is subject to inhibition as well as activation by hexose metabolites. Reporter gene experiments in Bacillus subtilis confirmed that this riboswitch integrates positive and negative chemical signals in its natural biological context. Contrary to the conventional view that a riboswitch responds to just a single cognate metabolite, our new model proposes that a single riboswitch integrates information from an array of chemical signals to modulate gene expression based on the overall metabolic state of the cell.

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Figure 1: System for measuring intracellular glmS riboswitch cleavage kinetics.
Figure 2: GlcN dependence of glmS riboswitch cleavage in yeast.
Figure 3: Chimeric mRNA cleavage and decay kinetics after transcription inhibition in different carbon sources.
Figure 4: Hexoses inhibit riboswitch cleavage in vitro and in Bacillus subtilis.
Figure 5: Model for riboswitch regulation of GlmS gene expression.

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Acknowledgements

This work was supported by US National Institutes of Health grant RO1 GM062277 (M.J.F.). P.Y.W. was supported by a graduate fellowship from The Skaggs Institute for Chemical Biology. We thank J. Pogliano for advice regarding the Bacillus subtilis experiments, J. Viladoms and M. Saha for assistance with plasmid constructions, and J.V. for critical reading of the manuscript.

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Authors and Affiliations

  1. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA

    Peter Y Watson & Martha J Fedor

  2. Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA, USA

    Peter Y Watson & Martha J Fedor

  3. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA

    Peter Y Watson & Martha J Fedor

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  1. Peter Y Watson
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  2. Martha J Fedor
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Contributions

P.Y.W. and M.J.F. conceived of and designed the experiments, analyzed the data and wrote the paper. P.Y.W. conducted the experiments.

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Correspondence to Martha J Fedor.

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Watson, P., Fedor, M. The glmS riboswitch integrates signals from activating and inhibitory metabolites in vivo. Nat Struct Mol Biol 18, 359–363 (2011). https://doi.org/10.1038/nsmb.1989

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