An mRNA structure that controls gene expression by binding S-adenosylmethionine

Abstract

Riboswitches are metabolite-binding RNA structures that serve as genetic control elements for certain messenger RNAs. These RNA switches have been identified in all three kingdoms of life and are typically responsible for the control of genes whose protein products are involved in the biosynthesis, transport or utilization of the target metabolite. Herein, we report that a highly conserved RNA domain found in bacteria serves as a riboswitch that responds to the coenzyme S-adenosylmethionine (SAM) with remarkably high affinity and specificity. SAM riboswitches undergo structural reorganization upon introduction of SAM, and these allosteric changes regulate the expression of 26 genes in Bacillus subtilis. This and related findings indicate that direct interaction between small metabolites and allosteric mRNAs is an important and widespread form of genetic regulation in bacteria.

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Figure 1: The S Box is a structured RNA domain that binds SAM.
Figure 2: Binding affinity and molecular discrimination by a SAM-binding RNA.
Figure 3: Scatchard analysis of SAM binding by the yitJ aptamer indicates tight binding and the formation of a 1:1 metabolite–RNA complex.
Figure 4: Effects of RNA mutations on SAM binding and genetic control.
Figure 5: Metabolite-induced transcription termination of several mRNAs that carry a SAM riboswitch.
Figure 6: Bacilli species subtilis and anthracis bind SAM with different affinities.

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Acknowledgements

We thank J.K. Wickiser for assistance with the Scatchard analysis, other members of the Breaker laboratory for helpful discussions, and D. Söll at Yale University for the generous gift of B. subtilis strain 168. We also thank A. Miranker and B. Koo for assistance in confirming the purity of SAM using mass spectroscopy. This work was supported by grants from the US National Institutes of Health and the US National Science Foundation. R.R.B is also grateful for support from the David and Lucile Packard Foundation.

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Correspondence to Ronald R Breaker.

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Winkler, W., Nahvi, A., Sudarsan, N. et al. An mRNA structure that controls gene expression by binding S-adenosylmethionine. Nat Struct Mol Biol 10, 701–707 (2003). https://doi.org/10.1038/nsb967

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