Book of Abstracts: Albany 2005
Riboswitches are natural metabolite-binding RNAs that control gene expression in many bacterial species. They typically are found in the non-coding regions of certain messenger RNAs, and control gene expression by ligand-induced allosteric changes in RNA structure. Frequently, these shape changes are harnessed to modulate transcription elongation or transcription initiation. One riboswitch class uses metabolite binding to control the action of a self-cleaving ribozyme, and thus appears to control messenger RNA stability. In combination, these RNA genetic switches control as much as two percent of the genes in some bacterial species.
The most highly conserved portion of riboswitches is the metabolite-binding aptamer domain, whose sequence and structural features define each riboswitch class. Of the proven riboswitch classes, the shortest aptamer domain measures only 34 nucleotides while the largest requires approximately 200 nucleotides. Even the smaller riboswitch domains appear to be capable of functioning as complex genetic switches. For example, we recently identified a riboswitch that uses two ligand-binding domains to bind two glycine molecules. Together, these domains cooperate to function as a more ?digital? genetic switch, thus allowing the organism to control gene expression in response to small changes in the concentration of glycine. We also have evidence that some riboswitches are kinetically as opposed to thermodynamically driven. Our findings support the view that RNA is a versatile medium for the construction of complex genetic elements.
Riboswitch research in the Breaker Laboratory is supported by grants from the NIH, the NSF, and from DARPA.
Ronald R. Breaker
Department of Molecular