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Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP
N. Sudarsan,1E. R. Lee,2Z. Weinberg,2R. H. Moy,3J. N. Kim,2K. H. Link,1R. R. Breaker1,2,3*
Cyclic di-guanosine monophosphate (di-GMP) is a circular RNAdinucleotide that functions as a second messenger in diversespecies of bacteria to trigger wide-ranging physiological changes,including cell differentiation, conversion between motile andbiofilm lifestyles, and virulence gene expression. However,the mechanisms by which cyclic di-GMP regulates gene expressionhave remained a mystery. We found that cyclic di-GMP in manybacterial species is sensed by a riboswitch class in messengerRNA that controls the expression of genes involved in numerousfundamental cellular processes. A variety of cyclic di-GMP regulonsare revealed, including some riboswitches associated with virulencegene expression, pilus formation, and flagellum biosynthesis.In addition, sequences matching the consensus for cyclic di-GMPriboswitches are present in the genome of a bacteriophage.
1 Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. 2 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA. 3 Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
* To whom correspondence should be addressed. E-mail: ronald.breaker{at}yale.edu
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