Key result
Binding of c-di-GMP to a riboswitch in Clostridium difficile favors a conformation of the ribozyme that promotes splicing in the presence of GTP, stimulating downstream protein production.
Identification of a two-input gene-control system in C. difficile where a riboswitch regulates a self-splicing ribozyme in response to c-di-GMP and GTP.
Does not support clinical translation for C. difficile; leaves open riboswitch-targeted therapies pending validation in human models.
Riboswitch Revealed Short regulatory regions—riboswitches—are found in the messenger RNAs of many bacteria, plants, and fungi. They bind to small-molecule metabolites and, through switching between alternate RNA secondary structures, regulate the expression of the linked RNA. Lee et al. (p. 845 ) have identified a c-di-GMP (cyclic di-guanosyl-5′-monophosphate)–binding riboswitch in the bacterium Clostridium difficile that regulates the splicing of a group I self-splicing ribozyme. Binding of c-di-GMP to the riboswitch favors a conformation of the ribozyme that promotes splicing in the presence of guanosine triphosphate (as is typical for this class of ribozymes). Concomitantly, splicing promotes the formation of a ribosome binding site, thereby stimulating protein production from the downstream pathogenesis-related gene. This regulatory region may thus constitute a two-input gene-control system that reads the concentration of both GTP and c-di-GMP. Thus, not all group I self-splicing ribozymes represent selfish genetic elements.
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Lee et al. (2010) studied this question. c-di-GMP was evaluated on Splicing of a group I self-splicing ribozyme. Binding of c-di-GMP to a riboswitch in Clostridium difficile favors a conformation of the ribozyme that promotes splicing in the presence of GTP, stimulating downstream protein production.
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