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Science 329 (5993): 845-848

Copyright © 2010 by the American Association for the Advancement of Science

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

Elaine R. Lee,1,* Jenny L. Baker,2,* Zasha Weinberg,1,3 Narasimhan Sudarsan,1,3 Ronald R. Breaker1,3,4,{dagger}

Abstract: 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.

1 Department of Molecular, Cellular, and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520–8103, USA.
2 Department of Chemistry, Yale University, Box 208103, New Haven, CT 06520–8103, USA.
3 Howard Hughes Medical Institute, Yale University, Box 208103, New Haven, CT 06520–8103, USA.
4 Department of Molecular Biophysics and Biochemistry, Yale University, Box 208103, New Haven, CT 06520–8103, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ronald.breaker{at}yale.edu

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