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

Abstract

Riboswitches are RNA domains that alter gene expression in response to ligand binding. The structure of the Bacillus subtilis preQ1 ribsoswitch, which recognizes the conserved modified nucleobase preQ1, in complex with its ligand indicates how an RNA of only 34 nucleotides recognizes its ligand. 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.