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Adenine riboswitches and gene activation by disruption of a transcription terminator

Nature Structural & Molecular Biology volume 11, pages 29–35 (2004)Cite this article

Abstract

A class of riboswitches that recognizes guanine and discriminates against other purine analogs was recently identified. RNAs that carry the consensus sequence and structural features of guanine riboswitches are located in the 5′ untranslated region (UTR) of numerous prokaryotic genes, where they control the expression of proteins involved in purine salvage and biosynthesis. We report that three representatives of this riboswitch class bind adenine with values for apparent dissociation constant (apparent Kd) that are several orders of magnitude lower than those for binding guanine. Because preference for adenine is attributable to a single nucleotide substitution, the RNA most likely recognizes its ligand by forming a Watson-Crick base pair. In addition, the adenine riboswitch associated with the ydhL gene of Bacillus subtilis functions as a genetic 'on' switch, wherein adenine binding causes a structural rearrangement that precludes formation of an intrinsic transcription terminator stem.

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Figure 1: Guanine- and adenine-specific riboswitches.
Figure 2: Ligand specificity of five G box RNAs.
Figure 3: Binding affinity of the ydhL aptamer for adenine.
Figure 4: Specificity of molecular recognition by the adenine aptamer from ydhL.
Figure 5: Interconversion of guanine- and adenine-specific aptamers.
Figure 6: Model for the genetic control of ydhL by an adenine riboswitch and its function as a gene-activating element.

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Acknowledgements

We thank members of the Breaker laboratory for helpful discussions and especially W.C. Winkler for helpful comments on the manuscript. This work was supported by grants from the US National Institutes of Health (GM 559343; NHLBI-N01-HV-28186) and the US National Science Foundation (EIA-0129939; EIA-0323510; EIA-0324045). R.R.B is also grateful for support from the Hereditary Disease Foundation and from the David and Lucile Packard Foundation.

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  1. Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, 06520-8103, Connecticut, USA

    Maumita Mandal & Ronald R Breaker

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  1. Maumita Mandal
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Correspondence to Ronald R Breaker.

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Mandal, M., Breaker, R. Adenine riboswitches and gene activation by disruption of a transcription terminator. Nat Struct Mol Biol 11, 29–35 (2004). https://doi.org/10.1038/nsmb710

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