Riboswitches are small, structured RNA motifs commonly found in the 5'-untranslated regions of certain mRNAs. Each riboswitch class has evolved to selectively recognize a small molecule or ion and change the expression of associated genes. More than two dozen different riboswitch classes have been validated, including RNA motifs that respond to various ligands such as nucleobases, amino acids, coenzymes, second messengers, toxic anions, and other chemicals. The ligand identity of the majority of riboswitches can often be readily deduced by their genomic contexts, but for a few �orphan� riboswitch classes, ligand identification can be challenging. Some orphan riboswitch candidates are associated with many different genes, or with genes encoding proteins of unknown functions, which make ligand identification difficult. A metabolite-binding riboswitch candidate called ydaO was discovered in bacteria nearly a decade ago, but its ligand has remained unknown. This predicted riboswitch class ranks among the top ten most common metabolite-sensing RNAs known, and it is associated with numerous genes for cell wall metabolism, osmotic stress response, and sporulation. We report that members of this noncoding RNA class selectively respond to the recently-discovered bacterial second messenger cyclic di-adenosine monophosphate (c-di-AMP). A representative RNA from Bacillus subtilis binds c-di-AMP with an affinity that is more than one million fold higher than for the c-di-AMP precursor ATP and for the bacterial second messenger c-di-GMP. Our findings resolve the mystery regarding the ligand for this extremely common riboswitch class, and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP.

Riboswitch class for the bacterial second messenger c-di-AMP

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.