Cyclic-di-GMP Reaches Out into the Bacterial RNA World

The ubiquitous bacterial signaling molecule bis-(3'-5')-cyclic guanosine monophosphate (c-di-GMP) has brought second messenger signaling back onto the agenda of molecular microbiologists. This is due not only to its general role in promoting biofilm formation, but also to the increasingly diverse array of effector molecules bound by c-di-GMP and of the target processes affected. Effectors include diverse transcription factors and proteins that directly interact with complex cellular machineries, as well as RNA molecules that act as riboswitches to regulate transcriptional elongation or translation. This flexibility in c-di-GMP action enables it to control diverse molecular processes in bacterial cells. New evidence further extends this range to include a c-di-GMP riboswitch linked to a self-splicing intron that has been "domesticated" by its carrier, the pathogenic bacterium Clostridium difficile, to serve in the control of expression of a downstream gene.