Researchers have developed a synthetic small molecule that binds to a bacterial riboswitch to control gene expression. Bacterial riboswitches are add-on segments attached to some of the microbes’ mRNAs. Endogenous ligands bind to these riboswitches, causing conformational changes that then inhibit translation of the mRNA. For example, the endogenous metabolite flavin mononucleotide (FMN) controls the translation of some riboswitch-bearing mRNAs. Because of riboswitches’ ability to control gene expression, researchers see them as possible drug targets. Previous attempts to develop synthetic riboswitch ligands focused exclusively on structures that closely resembled endogenous metabolites—limiting the range of candidates normally required for drug development. By screening a library of about 57,000 synthetic small molecules with antibacterial activity, Terry Roemer of Merck Research Laboratories, in Kenilworth, N.J., and coworkers have now found a small molecule called ribocil that inhibits bacterial cell growth by acting as a ligand for an FMN riboswitch (Nature 2015, DOI: 10.1038/nature15542). The findings indicate that a wider range of small molecules than previously expected may be able to target riboswitches and other regulatory RNAs.