An Allosteric Self-Splicing Ribozyme Triggered by a Bacterial Second Messenger

• Published in: Science (American Association for the Advancement of Science) Vol. 329; no. 5993; pp. 845 - 848
• Main Authors: Lee, Elaine R., Baker, Jenny L., Weinberg, Zasha, Sudarsan, Narasimhan, Breaker, Ronald R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 13.08.2010; The American Association for the Advancement of Science
• Subjects: 5' Untranslated Regions; Aptamers, Nucleotide - chemistry; Bacteria; Bacteriology; Base Pairing; Base Sequence; Binding; Biological and medical sciences; Clostridioides difficile - genetics; Clostridioides difficile - metabolism; Clostridioides difficile - pathogenicity; Clostridium; Codon, Initiator; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Exons; Fundamental and applied biological sciences. Psychology; Genes; Genes, Bacterial; Genetic mutation; Genetics; Guanosine Triphosphate - metabolism; Joints; Messenger RNA; Microbiology; Molecular biology; Molecular Sequence Data; Nucleic Acid Conformation; Nucleotides; Regulators; Regulatory Sequences, Ribonucleic Acid; Ribonucleic acid; Ribonucleic acids; Ribosomes; Ribozymes; RNA; RNA precursors; RNA Splicing; RNA, Bacterial - chemistry; RNA, Bacterial - genetics; RNA, Bacterial - metabolism; RNA, Catalytic - chemistry; RNA, Catalytic - genetics; RNA, Catalytic - metabolism; RNA, Messenger - chemistry; RNA, Messenger - genetics; RNA, Messenger - metabolism; Second Messenger Systems; Second messengers; Splicing; Start codon; Virulence; Self-splicing; Molecular processing; RNA; Ribozyme; Clostridiaceae; Clostridium difficile; Second messenger; Clostridiales; Bacteria
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1190713

Group I self-splicing ribozymes commonly function as components of selfish mobile genetic elements. We identified an allosteric group I ribozyme, wherein self-splicing is regulated by a distinct riboswitch class that senses the bacterial second messenger c-di-GMP. The tandem RNA sensory system resides in the 5' untranslated region of the messenger RNA for a putative virulence gene in the pathogenic bacterium Clostridium difficile. c-di-GMP binding by the riboswitch induces folding changes at atypical splice site junctions to modulate alternative RNA processing.Our findings indicate that some self-splicing ribozymes are not selfish elements but are harnessed by cells as metabolite sensors and genetic regulators.