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able to discriminate against metabolites related to its natural ligand in order
to tightly regulate metabolic pathways. However, it has been demonstrated
that ligand analogs can substitute for the natural coenzyme, affording the
opportunity to artificially modulate glmS ribozyme/riboswitch activity
and metabolic gene expression, and ultimately inhibit bacterial growth. 45,46
Therefore, continued investigation of both ribozyme and riboswitch func-
tion of the glmS RNA may identify metabolite analogs as prospective anti-
microbial agents. The work described here underscores the importance of
biochemical and structural characterization of riboswitches to the task of
appropriately designing effective and efficient agonists or antagonists as anti-
biotics. If successful, this approach to altering gene expression within essen-
tial metabolic pathways will provide a novel means by which to target
specific pathogenic bacteria.
ACKNOWLEDGMENTS
I wish to thank Mark and Kay Delaney for their generous donation to my laboratory. This
publication was made possible by grants from the National Center for Research Resources
(5P20RR016469) and the National Institute for General Medical Science (NIGMS)
(5P20GM103427 and R15M083641), a component of the National Institutes of Health
(NIH) and its contents are the sole responsibility of the authors and do not necessarily
represent the official views of NIGMS or NIH. J. K. S. was supported by the Clare
Boothe Luce Endowed Chair for Women in Science, funded by the Luce Foundation.
REFERENCES
1. Paulsen IT, Banerjei L, Myers GS, et al. Role of mobile DNA in the evolution of
vancomycin-resistant Enterococcus faecalis . Science . 2003;299(5615):2071-2074.
2. Winkler WC, Nahvi A, Roth A, Collins JA, Breaker RR. Control of gene expression by
a natural metabolite-responsive ribozyme. Nature . 2004;428(6980):281-286.
3. Nudler E, Mironov AS. The riboswitch control of bacterial metabolism. Trends Biochem
Sci . 2004;29(1):11-17.
4. Winkler WC, Breaker RR. Regulation of bacterial gene expression by riboswitches.
Annu Rev Microbiol . 2005;59:487-517.
5. Collins JA, Irnov I, Baker S, Winkler WC. Mechanism of mRNA destabilization by the
glmS ribozyme. Genes Dev . 2007;21(24):3356-3368.
6. McCarthy TJ, Plog MA, Floy SA, Jansen JA, Soukup JK, Soukup GA. Ligand require-
ments for glmS ribozyme self-cleavage. Chem Biol . 2006;12(11):1221-1226.
7. Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A. Rfam: anno-
tating noncoding RNAs in complete genomes. Nucleic Acids Res . 2005;33(database
issue):D121-D124.
8. Griffiths-Jones S, Bateman A, Marshall M, Khanna A, Eddy SR. Rfam: an RNA family
database. Nucleic Acids Res . 2003;31(1):439-441.
9. Barrick JE, Corbino KA, Winkler WC, et al. New RNA motifs suggest an expanded
scope for riboswitches in bacterial genetic control. Proc Natl Acad Sci USA . 2004;101
(17):6421-6426.
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