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Structure of the S-adenosylmethionine riboswitch regulatory mRNA element

Abstract

Riboswitches are cis-acting genetic regulatory elements found in the 5′-untranslated regions of messenger RNAs that control gene expression through their ability to bind small molecule metabolites directly1,2. Regulation occurs through the interplay of two domains of the RNA: an aptamer domain that responds to intracellular metabolite concentrations and an expression platform that uses two mutually exclusive secondary structures to direct a decision-making process. In Gram-positive bacteria such as Bacillus species, riboswitches control the expression of more than 2% of all genes through their ability to respond to a diverse set of metabolites including amino acids, nucleobases and protein cofactors1,2. Here we report the 2.9-Å resolution crystal structure of an S-adenosylmethionine (SAM)-responsive riboswitch from Thermoanaerobacter tengcongensis complexed with S-adenosylmethionine, an RNA element that controls the expression of several genes involved in sulphur and methionine metabolism3,4,5,6. This RNA folds into a complex three-dimensional architecture that recognizes almost every functional group of the ligand through a combination of direct and indirect readout mechanisms. Ligand binding induces the formation of a series of tertiary interactions with one of the helices, serving as a communication link between the aptamer and expression platform domains.

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Figure 1: Secondary and tertiary structure of the SAM-I riboswitch.
Figure 2: Comparison of the global architecture of the Azoarcus group I intron and the SAM-I riboswitch.
Figure 3: Detailed view of the tertiary architecture of the pseudoknot region.
Figure 4: Detailed view of SAM recognition by the riboswitch.

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Acknowledgements

We thank S. Edwards for managing the CU Boulder X-ray crystallography facility, the staff at ALS beamline 8.2.1 for assistance, and A. Pardi, T. Cech, R. Breaker, W. Winkler, B. Golden, J. Kieft and A. Ke for discussions. This work was supported by grants from the National Institutes of Health and the W. M. Keck Foundation Initiative in RNA Science at the University of Colorado (R.T.B.) and a National Institutes of Health Predoctoral Training Grant (R.K.M.).

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Correspondence to Robert T. Batey.

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The atomic coordinates and structure factors have been deposited in the Protein Data Bank with the accession number 2GIS. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods (outlining the experimental techniques used for the crystallization, data collection and refinement of the SAM-I model), Supplementary Table 1, Supplementary Figures 1–5 and additional references. (DOC 4233 kb)

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Montange, R., Batey, R. Structure of the S-adenosylmethionine riboswitch regulatory mRNA element. Nature 441, 1172–1175 (2006). https://doi.org/10.1038/nature04819

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