Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 321 (5887): 411-413

Copyright © 2008 by the American Association for the Advancement of Science

Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP

N. Sudarsan,1 E. R. Lee,2 Z. Weinberg,2 R. H. Moy,3 J. N. Kim,2 K. H. Link,1 R. R. Breaker1,2,3*

Abstract: Cyclic di-guanosine monophosphate (di-GMP) is a circular RNA dinucleotide that functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes, including cell differentiation, conversion between motile and biofilm lifestyles, and virulence gene expression. However, the mechanisms by which cyclic di-GMP regulates gene expression have remained a mystery. We found that cyclic di-GMP in many bacterial species is sensed by a riboswitch class in messenger RNA that controls the expression of genes involved in numerous fundamental cellular processes. A variety of cyclic di-GMP regulons are revealed, including some riboswitches associated with virulence gene expression, pilus formation, and flagellum biosynthesis. In addition, sequences matching the consensus for cyclic di-GMP riboswitches 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


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Structural determinants for ligand capture by a class II preQ1 riboswitch.
M. Kang, C. D. Eichhorn, and J. Feigon (2014)
PNAS 111, E663-E671
   Abstract »    Full Text »    PDF »
CelR, an Ortholog of the Diguanylate Cyclase PleD of Caulobacter, Regulates Cellulose Synthesis in Agrobacterium tumefaciens.
D. M. Barnhart, S. Su, B. E. Baccaro, L. M. Banta, and S. K. Farrand (2013)
Appl. Envir. Microbiol. 79, 7188-7202
   Abstract »    Full Text »    PDF »
The Second Messenger Cyclic Di-GMP Regulates Clostridium difficile Toxin Production by Controlling Expression of sigD.
R. W. McKee, M. R. Mangalea, E. B. Purcell, E. K. Borchardt, and R. Tamayo (2013)
J. Bacteriol. 195, 5174-5185
   Abstract »    Full Text »    PDF »
The Characterization of a Cyclic-Di-GMP (c-Di-GMP) Pathway Leads to a New Tool for Studying c-Di-GMP Metabolic Genes.
R. Tamayo (2013)
J. Bacteriol. 195, 4779-4781
   Full Text »    PDF »
Functional Characterization of Core Components of the Bacillus subtilis Cyclic-Di-GMP Signaling Pathway.
X. Gao, S. Mukherjee, P. M. Matthews, L. A. Hammad, D. B. Kearns, and C. E. Dann III (2013)
J. Bacteriol. 195, 4782-4792
   Abstract »    Full Text »    PDF »
PdeB, a Cyclic Di-GMP-Specific Phosphodiesterase That Regulates Shewanella oneidensis MR-1 Motility and Biofilm Formation.
L. Chao, S. Rakshe, M. Leff, and A. M. Spormann (2013)
J. Bacteriol. 195, 3827-3833
   Abstract »    Full Text »    PDF »
RNA-Mediated Regulation in Pathogenic Bacteria.
I. Caldelari, Y. Chao, P. Romby, and J. Vogel (2013)
Cold Spring Harb Perspect Med 3, a010298
   Abstract »    Full Text »    PDF »
The agr Locus Regulates Virulence and Colonization Genes in Clostridium difficile 027.
M. J. Martin, S. Clare, D. Goulding, A. Faulds-Pain, L. Barquist, H. P. Browne, L. Pettit, G. Dougan, T. D. Lawley, and B. W. Wren (2013)
J. Bacteriol. 195, 3672-3681
   Abstract »    Full Text »    PDF »
The EAL domain protein YciR acts as a trigger enzyme in a c-di-GMP signalling cascade in E. coli biofilm control.
S. Lindenberg, G. Klauck, C. Pesavento, E. Klauck, and R. Hengge (2013)
EMBO J. 32, 2001-2014
   Abstract »    Full Text »    PDF »
Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs.
Y. Shu, F. Haque, D. Shu, W. Li, Z. Zhu, M. Kotb, Y. Lyubchenko, and P. Guo (2013)
RNA 19, 767-777
   Abstract »    Full Text »    PDF »
Exoprotein Production Correlates with Morphotype Changes of Nonmotile Shewanella oneidensis Mutants.
M. Shi, L. Wu, Y. Xia, H. Chen, Q. Luo, L. Sun, and H. Gao (2013)
J. Bacteriol. 195, 1463-1474
   Abstract »    Full Text »    PDF »
Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger.
U. Romling, M. Y. Galperin, and M. Gomelsky (2013)
Microbiol. Mol. Biol. Rev. 77, 1-52
   Abstract »    Full Text »    PDF »
Modulation of quaternary structure and enhancement of ligand binding by the K-turn of tandem glycine riboswitches.
N. J. Baird and A. R. Ferre-D'Amare (2013)
RNA 19, 167-176
   Abstract »    Full Text »    PDF »
Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose.
V. Zorraquino, B. Garcia, C. Latasa, M. Echeverz, A. Toledo-Arana, J. Valle, I. Lasa, and C. Solano (2013)
J. Bacteriol. 195, 417-428
   Abstract »    Full Text »    PDF »
The expression platform and the aptamer: cooperativity between Mg2+ and ligand in the SAM-I riboswitch.
S. P. Hennelly, I. V. Novikova, and K. Y. Sanbonmatsu (2013)
Nucleic Acids Res. 41, 1922-1935
   Abstract »    Full Text »    PDF »
Transcriptomic profiling of the oyster pathogen Vibrio splendidus opens a window on the evolutionary dynamics of the small RNA repertoire in the Vibrio genus.
C. Toffano-Nioche, A. N. Nguyen, C. Kuchly, A. Ott, D. Gautheret, P. Bouloc, and A. Jacq (2012)
RNA 18, 2201-2219
   Abstract »    Full Text »    PDF »
LtmA, a novel cyclic di-GMP-responsive activator, broadly regulates the expression of lipid transport and metabolism genes in Mycobacterium smegmatis.
W. Li and Z.-G. He (2012)
Nucleic Acids Res. 40, 11292-11307
   Abstract »    Full Text »    PDF »
Evidence for Cyclic Di-GMP-Mediated Signaling in Bacillus subtilis.
Y. Chen, Y. Chai, J.-h. Guo, and R. Losick (2012)
J. Bacteriol. 194, 5080-5090
   Abstract »    Full Text »    PDF »
Structures of the PelD Cyclic Diguanylate Effector Involved in Pellicle Formation in Pseudomonas aeruginosa PAO1.
Z. Li, J.-H. Chen, Y. Hao, and S. K. Nair (2012)
J. Biol. Chem. 287, 30191-30204
   Abstract »    Full Text »    PDF »
The FleQ protein from Pseudomonas aeruginosa functions as both a repressor and an activator to control gene expression from the pel operon promoter in response to c-di-GMP.
C. Baraquet, K. Murakami, M. R. Parsek, and C. S. Harwood (2012)
Nucleic Acids Res. 40, 7207-7218
   Abstract »    Full Text »    PDF »
Cyclic Diguanylate Inversely Regulates Motility and Aggregation in Clostridium difficile.
E. B. Purcell, R. W. McKee, S. M. McBride, C. M. Waters, and R. Tamayo (2012)
J. Bacteriol. 194, 3307-3316
   Abstract »    Full Text »    PDF »
A rapid assay for affinity and kinetics of molecular interactions with nucleic acids.
G. P. Donaldson, K. G. Roelofs, Y. Luo, H. O. Sintim, and V. T. Lee (2012)
Nucleic Acids Res. 40, e48
   Abstract »    Full Text »    PDF »
Output Targets and Transcriptional Regulation by a Cyclic Dimeric GMP-Responsive Circuit in the Vibrio parahaemolyticus Scr Network.
R. B. R. Ferreira, D. M. Chodur, L. C. M. Antunes, M. J. Trimble, and L. L. McCarter (2012)
J. Bacteriol. 194, 914-924
   Abstract »    Full Text »    PDF »
Attenuation of loop-receptor interactions with pseudoknot formation.
K. A. Afonin, Y.-P. Lin, E. R. Calkins, and L. Jaeger (2012)
Nucleic Acids Res. 40, 2168-2180
   Abstract »    Full Text »    PDF »
Riboswitches and the RNA World.
R. R. Breaker (2012)
Cold Spring Harb Perspect Biol 4, a003566
   Abstract »    Full Text »    PDF »
Widespread Genetic Switches and Toxicity Resistance Proteins for Fluoride.
J. L. Baker, N. Sudarsan, Z. Weinberg, A. Roth, R. B. Stockbridge, and R. R. Breaker (2012)
Science 335, 233-235
   Abstract »    Full Text »    PDF »
N-Acetylglucosamine-dependent biofilm formation in Pectobacterium atrosepticum is cryptic and activated by elevated c-di-GMP levels.
D. Perez-Mendoza, S. J. Coulthurst, J. Sanjuan, and G. P. C. Salmond (2011)
Microbiology 157, 3340-3348
   Abstract »    Full Text »    PDF »
Mechanism for gene control by a natural allosteric group I ribozyme.
A. G. Y. Chen, N. Sudarsan, and R. R. Breaker (2011)
RNA 17, 1967-1972
   Abstract »    Full Text »    PDF »
Brucella melitensis Cyclic di-GMP Phosphodiesterase BpdA Controls Expression of Flagellar Genes.
E. Petersen, P. Chaudhuri, C. Gourley, J. Harms, and G. Splitter (2011)
J. Bacteriol. 193, 5683-5691
   Abstract »    Full Text »    PDF »
Molecular Signaling Mechanisms of the Periopathogen, Treponema denticola.
J. R. Frederick, J. Sarkar, J. V. McDowell, and R. T. Marconi (2011)
Journal of Dental Research 90, 1155-1163
   Abstract »    PDF »
Analysis of the HD-GYP Domain Cyclic Dimeric GMP Phosphodiesterase Reveals a Role in Motility and the Enzootic Life Cycle of Borrelia burgdorferi.
S. Z. Sultan, J. E. Pitzer, T. Boquoi, G. Hobbs, M. R. Miller, and M. A. Motaleb (2011)
Infect. Immun. 79, 3273-3283
   Abstract »    Full Text »    PDF »
Identification and Characterization of CdgB, a Diguanylate Cyclase Involved in Developmental Processes in Streptomyces coelicolor.
N. T. Tran, C. D. Den Hengst, J. P. Gomez-Escribano, and M. J. Buttner (2011)
J. Bacteriol. 193, 3100-3108
   Abstract »    Full Text »    PDF »
Riboswitches: Structures and Mechanisms.
A. D. Garst, A. L. Edwards, and R. T. Batey (2011)
Cold Spring Harb Perspect Biol 3, a003533
   Abstract »    Full Text »    PDF »
Structural basis of differential ligand recognition by two classes of bis-(3'-5')-cyclic dimeric guanosine monophosphate-binding riboswitches.
K. D. Smith, C. A. Shanahan, E. L. Moore, A. C. Simon, and S. A. Strobel (2011)
PNAS 108, 7757-7762
   Abstract »    Full Text »    PDF »
Analysis of the Borrelia burgdorferi Cyclic-di-GMP-Binding Protein PlzA Reveals a Role in Motility and Virulence.
J. E. Pitzer, S. Z. Sultan, Y. Hayakawa, G. Hobbs, M. R. Miller, and M. A. Motaleb (2011)
Infect. Immun. 79, 1815-1825
   Abstract »    Full Text »    PDF »
Identification of a Chitin-Induced Small RNA That Regulates Translation of the tfoX Gene, Encoding a Positive Regulator of Natural Competence in Vibrio cholerae.
S. Yamamoto, H. Izumiya, J. Mitobe, M. Morita, E. Arakawa, M. Ohnishi, and H. Watanabe (2011)
J. Bacteriol. 193, 1953-1965
   Abstract »    Full Text »    PDF »
Cyclic Diguanylate Signaling Proteins Control Intracellular Growth of Legionella pneumophila.
A. Levi, M. Folcher, U. Jenal, and H. A. Shuman (2011)
mBio 2, e00316-10
   Abstract »    Full Text »    PDF »
Identification of a tertiary interaction important for cooperative ligand binding by the glycine riboswitch.
T. V. Erion and S. A. Strobel (2011)
RNA 17, 74-84
   Abstract »    Full Text »    PDF »
Cyclic-di-GMP Reaches Out into the Bacterial RNA World.
R. Hengge (2010)
Science Signaling 3, pe44
   Abstract »    Full Text »    PDF »
Comparative genomics of cyclic-di-GMP signalling in bacteria: post-translational regulation and catalytic activity.
A. S. N. Seshasayee, G. M. Fraser, and N. M. Luscombe (2010)
Nucleic Acids Res. 38, 5970-5981
   Abstract »    Full Text »    PDF »
The diguanylate cyclase YddV controls production of the exopolysaccharide poly-N-acetylglucosamine (PNAG) through regulation of the PNAG biosynthetic pgaABCD operon.
L. Tagliabue, D. Antoniani, A. Maciag, P. Bocci, N. Raffaelli, and P. Landini (2010)
Microbiology 156, 2901-2911
   Abstract »    Full Text »    PDF »
Identification and Characterization of a Phosphodiesterase That Inversely Regulates Motility and Biofilm Formation in Vibrio cholerae.
X. Liu, S. Beyhan, B. Lim, R. G. Linington, and F. H. Yildiz (2010)
J. Bacteriol. 192, 4541-4552
   Abstract »    Full Text »    PDF »
An Allosteric Self-Splicing Ribozyme Triggered by a Bacterial Second Messenger.
E. R. Lee, J. L. Baker, Z. Weinberg, N. Sudarsan, and R. R. Breaker (2010)
Science 329, 845-848
   Abstract »    Full Text »    PDF »
Evidence for Widespread Gene Control Function by the ydaO Riboswitch Candidate.
K. F. Block, M. C. Hammond, and R. R. Breaker (2010)
J. Bacteriol. 192, 3983-3989
   Abstract »    Full Text »    PDF »
Asymmetrical Distribution of the Second Messenger c-di-GMP upon Bacterial Cell Division.
M. Christen, H. D. Kulasekara, B. Christen, B. R. Kulasekara, L. R. Hoffman, and S. I. Miller (2010)
Science 328, 1295-1297
   Abstract »    Full Text »    PDF »
Transcription attenuation in bacteria: theme and variations.
M. Naville, D. Gautheret, M. Naville, and D. Gautheret (2010)
Briefings in Functional Genomics 9, 178-189
   Abstract »    Full Text »    PDF »
Mining regulatory 5'UTRs from cDNA deep sequencing datasets.
J. Livny and M. K. Waldor (2010)
Nucleic Acids Res. 38, 1504-1514
   Abstract »    Full Text »    PDF »
Vibrio cholerae VpsT Regulates Matrix Production and Motility by Directly Sensing Cyclic di-GMP.
P. V. Krasteva, J. C. N. Fong, N. J. Shikuma, S. Beyhan, M. V. A. S. Navarro, F. H. Yildiz, and H. Sondermann (2010)
Science 327, 866-868
   Abstract »    Full Text »    PDF »
Bacteriophage-Mediated Toxin Gene Regulation in Clostridium difficile.
R. Govind, G. Vediyappan, R. D. Rolfe, B. Dupuy, and J. A. Fralick (2009)
J. Virol. 83, 12037-12045
   Abstract »    Full Text »    PDF »
Cyclic-di-GMP-Binding CRP-Like Protein: a Spectacular New Role for a Veteran Signal Transduction Actor.
M. Gomelsky (2009)
J. Bacteriol. 191, 6785-6787
   Full Text »    PDF »
Transcription attenuation in bacteria: theme and variations.
M. Naville and D. Gautheret (2009)
Briefings in Functional Genomics 8, 482-492
   Abstract »    Full Text »    PDF »
Signals, Regulatory Networks, and Materials That Build and Break Bacterial Biofilms.
E. Karatan and P. Watnick (2009)
Microbiol. Mol. Biol. Rev. 73, 310-347
   Abstract »    Full Text »    PDF »
Genetic reductionist approach for dissecting individual roles of GGDEF proteins within the c-di-GMP signaling network in Salmonella.
C. Solano, B. Garcia, C. Latasa, A. Toledo-Arana, V. Zorraquino, J. Valle, J. Casals, E. Pedroso, and I. Lasa (2009)
PNAS 106, 7997-8002
   Abstract »    Full Text »    PDF »
Gene expression patterns and differential input into curli fimbriae regulation of all GGDEF/EAL domain proteins in Escherichia coli.
N. Sommerfeldt, A. Possling, G. Becker, C. Pesavento, N. Tschowri, and R. Hengge (2009)
Microbiology 155, 1318-1331
   Abstract »    Full Text »    PDF »
The Anaplasma phagocytophilum PleC Histidine Kinase and PleD Diguanylate Cyclase Two-Component System and Role of Cyclic Di-GMP in Host Cell Infection.
T.-H. Lai, Y. Kumagai, M. Hyodo, Y. Hayakawa, and Y. Rikihisa (2009)
J. Bacteriol. 191, 693-700
   Abstract »    Full Text »    PDF »
Cyclic Di-GMP (c-Di-GMP) Goes in1593to Host Cells--c-Di-GMP Signaling in the Obligate Intracellular Pathogen Anaplasma phagocytophilum.
U. Romling (2009)
J. Bacteriol. 191, 683-686
   Full Text »    PDF »
Riboswitch RNAs: using RNA to sense cellular metabolism.
T. M. Henkin (2008)
Genes & Dev. 22, 3383-3390
   Abstract »    Full Text »    PDF »
Identification and Characterization of Cyclic Diguanylate Signaling Systems Controlling Rugosity in Vibrio cholerae.
S. Beyhan, L. S. Odell, and F. H. Yildiz (2008)
J. Bacteriol. 190, 7392-7405
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882