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

Narasimhan Sudarsan; J. Kenneth Wickiser; Shingo Nakamura; Margaret S. Ebert; Ronald R. Breaker

doi:10.1101/gad.1140003

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

¹ Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520-8103, USA
² Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520-8103, USA

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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Footnotes

Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1140003.
↵3 Corresponding author. E-MAIL ronald.breaker{at}yale.edu; FAX (203) 432-6604.
- Accepted September 9, 2003.
- Received August 4, 2003.
Cold Spring Harbor Laboratory Press