ScienceDaily (Aug. 12, 2010) — Within a dangerous stomach bacterium, Yale University researchers have discovered an ancient but functioning genetic remnant from a time before DNA existed, they report in the August 13 issue of the journal Science.
This micrograph depicts Gram-positive C. difficile bacteria. (Credit: CDC / Janice Carr)
To the surprise of researchers, this RNA complex seems to play a critical role in the ability of the organism to infect human cells, a job carried out almost exclusively by proteins produced from DNA's instruction manual.
"What these cells are doing is using ancient RNA technology to control modern gene expression," said Ron Breaker, the Henry Ford II Professor of Molecular, Cellular and Developmental Biology at Yale, investigator for the Howard Hughes Medical Institute and senior author of the study.
In old textbooks, RNA was viewed simply as the chemical intermediary between DNA's instruction manual and the creation of proteins. However, Breaker's lab has identified the existence and function of riboswitches, or RNA structures that have the ability to detect molecules and control gene expression -- an ability once believed to be possessed solely by proteins. Breaker and many other scientists now believe the first forms of life depended upon such RNA machines, which would have had to find ways to interact and carry out many of the functions proteins do today.
The new paper describes the complex interactions of two small RNA molecules and two larger RNA molecules that together influence the function of a self-splicing ribozyme, a structure many biologists had believed had no role other than to reproduce itself. The new study, however, suggests that in the pathogenic stomach bacterium Clostridium difficile, this RNA structure acts as a sort of sensor to help regulate the expression of genes, probably to help the bacterium manipulate human cells.
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Science 13 August 2010:
Vol. 329. no. 5993, pp. 845 - 848
DOI: 10.1126/science.1190713
An Allosteric Self-Splicing Ribozyme Triggered by a Bacterial Second Messenger
Vol. 329. no. 5993, pp. 845 - 848
DOI: 10.1126/science.1190713
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,
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.
To whom correspondence should be addressed. E-mail: ronald.breaker@yale.edu
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.
To whom correspondence should be addressed. E-mail: ronald.breaker@yale.edu
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