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Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold

Abstract

PreQ1 riboswitches regulate genes by binding the pyrrolopyrimidine intermediate preQ1 during the biosynthesis of the essential tRNA base queuosine. We report what is to our knowledge the first preQ1-II riboswitch structure at 2.3-Å resolution, which uses a previously uncharacterized fold to achieve effector recognition at the confluence of a three-way helical junction flanking a pseudoknotted ribosome-binding site. The results account for translational control mediated by the preQ1-II riboswitch class and expand the known repertoire of ligand-binding modes used by regulatory RNAs.

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Figure 1: Queuosine biosynthesis, secondary structure and tertiary fold of the L. rhamnosus preQ1-II riboswitch.
Figure 2: Architecture of the effector binding site and tertiary interactions involved in preQ1-II riboswitch ligand recognition.

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Acknowledgements

We thank J. Jenkins, D. Turner and C. Kielkopf for suggestions and V. Bandarian for preQ0. J.A.L. was funded by US National Institutes of Health (NIH) grant T32 GM068411 and a Hooker fellowship. This research was funded by NIH grants RR026501 and GM063162 to J.E.W. Portions of this research were conducted at the Stanford Synchrotron Radiation Lightsource, which is funded by the US Department of Energy and NIH grants GM103393 and RR001209.

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Contributions

M.S. identified the L. rhamnosus riboswitch, produced RNA and conducted in-line probing; J.K. and J.A.L. grew crystals; J.A.L. conducted isothermal titration calorimetry, interpreted in-line probing and solved the structure. J.E.W. supervised the project. J.A.L. and J.E.W. prepared the manuscript.

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Correspondence to Joseph E Wedekind.

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The authors declare no competing financial interests.

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Liberman, J., Salim, M., Krucinska, J. et al. Structure of a class II preQ1 riboswitch reveals ligand recognition by a new fold. Nat Chem Biol 9, 353–355 (2013). https://doi.org/10.1038/nchembio.1231

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