Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase

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Riboswitches are mRNA domains that bind metabolites and modulate gene expression in cis. We report cocrystal structures of a remarkably compact riboswitch (34 nucleotides suffice for ligand recognition) from Bacillus subtilis that is selective for the essential nucleobase preQ1 (7-aminomethyl-7-deazaguanine). The structures reveal a previously unrecognized pseudoknot fold and suggest a conserved gene-regulatory mechanism whereby ligand binding promotes sequestration of an RNA segment that otherwise assembles into a transcriptional antiterminator.

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Figure 1: PreQ1 riboswitch structure.
Figure 2: PreQ1 recognition and control of gene expression.

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We thank the staff of Advanced Light Source (ALS) beamline 5.0.1 and J. Bolduc for assistance with synchrotron and home laboratory data collection, respectively, R. Huang (University of Illinois at Urbana-Champaign) for his gift of preQ1, and N. Baird, T. Hamma, C. Hoang, N. Kulshina, J. Pitt, J. Posakony, A. Roll-Mecak and H. Xiao for discussions. This work was supported by grants from the Damon Runyon Cancer Research Foundation (DRG-1863-05 to D.J.K. and DRG-1844-04 to T.E.E.), the Howard Hughes Medical Institute (A.R.F.-D.), the US National Institutes of Health (K99 GM084076-01 to D.J.K.) and the W.M. Keck Foundation (A.R.F.-D.).

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Correspondence to Adrian R Ferré-D'Amaré.

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Supplementary Figures 1–5, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 5258 kb)

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