An mRNA structure in bacteria that controls gene expression by binding lysine

Narasimhan Sudarsan(Yale University), J. Kenneth Wickiser(Yale University), Shingo Nakamura(Institut thématique Génétique, génomique et bioinformatique), Margaret S. Ebert(Institut thématique Génétique, génomique et bioinformatique), Ronald R. Breaker(Institut thématique Génétique, génomique et bioinformatique)
Genes & Development
November 1, 2003
Cited by 368Open Access
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Abstract

Riboswitches are metabolite-responsive genetic control elements that reside in the untranslated regions (UTRs) of certain messenger RNAs. Herein, we report that the 5′-UTR of the lysC gene of Bacillus subtilis carries a conserved RNA element that serves as a lysine-responsive riboswitch. The ligand-binding domain of the riboswitch binds to L-lysine with an apparent dissociation constant (K D ) of ∼1 µM, and exhibits a high level of molecular discrimination against closely related analogs, including D-lysine and ornithine. Furthermore, we provide evidence that this widespread class of riboswitches serves as a target for the antimetabolite S -(2-aminoethyl)-L-cysteine (AEC). These findings add support to the hypotheses that direct sensing of metabolites by messenger RNAs is a fundamental form of genetic control and that riboswitches represent a new class of antimicrobial drug targets.


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