title: The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch.
abstract: Riboswitches are genetic control elements that usually reside in untranslated regions of messenger RNAs. These folded RNAs directly bind metabolites and undergo allosteric changes that modulate gene expression. A flavin mononucleotide (FMN)-dependent riboswitch from the ribDEAHT operon of Bacillus subtilis uses a transcription termination mechanism wherein formation of an RNA-FMN complex causes formation of an intrinsic terminator stem. We assessed the importance of RNA transcription speed and the kinetics of FMN binding to the nascent mRNA for riboswitch function. The riboswitch does not attain thermodynamic equilibrium with FMN before RNA polymerase needs to make a choice between continued transcription and transcription termination. Therefore, this riboswitch is kinetically driven, and functions more like a "molecular fuse." This reliance on the kinetics of ligand association and RNA polymerization speed might be common for riboswitches that utilize transcription termination mechanisms.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: J Kenneth
authors.initials: JK
authors.lastname: Wickiser
authors.forename: Wade C
authors.initials: WC
authors.lastname: Winkler
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Breaker
authors.forename: Donald M
authors.initials: DM
authors.lastname: Crothers
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics*; D001483:Base Sequence; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D005486:Flavin Mononucleotide / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009876:Operon / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D013728:Terminator Regions, Genetic; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D012329:RNA, Bacterial; D012333:RNA, Messenger; D005486:Flavin Mononucleotide; D012321:DNA-Directed RNA Polymerases