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Science 306 (5694): 275-279

Copyright © 2004 by the American Association for the Advancement of Science

A Glycine-Dependent Riboswitch That Uses Cooperative Binding to Control Gene Expression

Maumita Mandal,1 Mark Lee,2 Jeffrey E. Barrick,2 Zasha Weinberg,3 Gail Mitchell Emilsson,1 Walter L. Ruzzo,3,4 Ronald R. Breaker1*

Abstract: We identified a previously unknown riboswitch class in bacteria that is selectively triggered by glycine. A representative of these glycine-sensing RNAs from Bacillus subtilis operates as a rare genetic on switch for the gcvT operon, which codes for proteins that form the glycine cleavage system. Most glycine riboswitches integrate two ligand-binding domains that function cooperatively to more closely approximate a two-state genetic switch. This advanced form of riboswitch may have evolved to ensure that excess glycine is efficiently used to provide carbon flux through the citric acid cycle and maintain adequate amounts of the amino acid for protein synthesis. Thus, riboswitches perform key regulatory roles and exhibit complex performance characteristics that previously had been observed only with protein factors.

1 Department of Molecular, Cellular, and Developmental Biology, Yale University, Post Office Box 208103, New Haven, CT 06520–8103, USA.
2 Department of Molecular Biophysics and Biochemistry, Yale University, Post Office Box 208103, New Haven, CT 06520–8103, USA.
3 Department of Computer Science and Engineering, University of Washington, Post Office Box 352350, Seattle, WA 98195, USA.
4 Department of Genome Sciences, University of Washington, Post Office Box 352350, Seattle, WA 98195, USA.

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

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   Abstract »    Full Text »    PDF »
Two-codon T-box riboswitch binding two tRNAs.
N. Y. Saad, V. Stamatopoulou, M. Braye, D. Drainas, C. Stathopoulos, and H. D. Becker (2013)
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   Abstract »    Full Text »    PDF »
Loop-loop interaction in an adenine-sensing riboswitch: A molecular dynamics study.
O. Allner, L. Nilsson, and A. Villa (2013)
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   Abstract »    Full Text »    PDF »
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S. Mujahid, R. H. Orsi, P. Vangay, K. J. Boor, and M. Wiedmann (2013)
Microbiology 159, 1109-1119
   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 »
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 »
Analysis of lysine recognition and specificity of the Bacillus subtilis L box riboswitch.
S. N. Wilson-Mitchell, F. J. Grundy, and T. M. Henkin (2012)
Nucleic Acids Res. 40, 5706-5717
   Abstract »    Full Text »    PDF »
RNA-Puzzles: A CASP-like evaluation of RNA three-dimensional structure prediction.
J. A. Cruz, M.-F. Blanchet, M. Boniecki, J. M. Bujnicki, S.-J. Chen, S. Cao, R. Das, F. Ding, N. V. Dokholyan, S. C. Flores, et al. (2012)
RNA 18, 610-625
   Abstract »    Full Text »    PDF »
Multiple conformations of SAM-II riboswitch detected with SAXS and NMR spectroscopy.
B. Chen, X. Zuo, Y.-X. Wang, and T. K. Dayie (2012)
Nucleic Acids Res. 40, 3117-3130
   Abstract »    Full Text »    PDF »
An energetically beneficial leader-linker interaction abolishes ligand-binding cooperativity in glycine riboswitches.
E. M. Sherman, J. Esquiaqui, G. Elsayed, and J.-D. Ye (2012)
RNA 18, 496-507
   Abstract »    Full Text »    PDF »
Riboswitches and the RNA World.
R. R. Breaker (2012)
Cold Spring Harb Perspect Biol 4, a003566
   Abstract »    Full Text »    PDF »
Direct structural analysis of modified RNA by fluorescent in-line probing.
B. Strauss, A. Nierth, M. Singer, and A. Jaschke (2012)
Nucleic Acids Res. 40, 861-870
   Abstract »    Full Text »    PDF »
Improvement of the crystallizability and expression of an RNA crystallization chaperone.
P. P. Ravindran, A. Heroux, and J.-D. Ye (2011)
J. Biochem. 150, 535-543
   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 »
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 »
Inducible gene expression from the plastid genome by a synthetic riboswitch.
A. Verhounig, D. Karcher, and R. Bock (2010)
PNAS 107, 6204-6209
   Abstract »    Full Text »    PDF »
Dissecting electrostatic screening, specific ion binding, and ligand binding in an energetic model for glycine riboswitch folding.
J. Lipfert, A. Y.L. Sim, D. Herschlag, and S. Doniach (2010)
RNA 16, 708-719
   Abstract »    Full Text »    PDF »
Atomistic basis for the on-off signaling mechanism in SAM-II riboswitch.
J. M. Kelley and D. Hamelberg (2010)
Nucleic Acids Res. 38, 1392-1400
   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 »
A variant riboswitch aptamer class for S-adenosylmethionine common in marine bacteria.
E. Poiata, M. M. Meyer, T. D. Ames, and R. R. Breaker (2009)
RNA 15, 2046-2056
   Abstract »    Full Text »    PDF »
MD simulations of ligand-bound and ligand-free aptamer: Molecular level insights into the binding and switching mechanism of the add A-riboswitch.
M. Sharma, G. Bulusu, and A. Mitra (2009)
RNA 15, 1673-1692
   Abstract »    Full Text »    PDF »
Identification and Gene Disruption of Small Noncoding RNAs in Streptomyces griseus.
T. Tezuka, H. Hara, Y. Ohnishi, and S. Horinouchi (2009)
J. Bacteriol. 191, 4896-4904
   Abstract »    Full Text »    PDF »
Biochemical Features and Functional Implications of the RNA-Based T-Box Regulatory Mechanism.
A. Gutierrez-Preciado, T. M. Henkin, F. J. Grundy, C. Yanofsky, and E. Merino (2009)
Microbiol. Mol. Biol. Rev. 73, 36-61
   Abstract »    Full Text »    PDF »
A flow cytometry-based screen for synthetic riboswitches.
S. A. Lynch and J. P. Gallivan (2009)
Nucleic Acids Res. 37, 184-192
   Abstract »    Full Text »    PDF »
Riboswitch RNAs: using RNA to sense cellular metabolism.
T. M. Henkin (2008)
Genes & Dev. 22, 3383-3390
   Abstract »    Full Text »    PDF »
Higher-Order Cellular Information Processing with Synthetic RNA Devices.
M. N. Win and C. D. Smolke (2008)
Science 322, 456-460
   Abstract »    Full Text »    PDF »
Riboswitch effectors as protein enzyme cofactors.
J. C. Cochrane and S. A. Strobel (2008)
RNA 14, 993-1002
   Abstract »    Full Text »    PDF »
Comparative genomic analysis of T-box regulatory systems in bacteria.
A. G. Vitreschak, A. A. Mironov, V. A. Lyubetsky, and M. S. Gelfand (2008)
RNA 14, 717-735
   Abstract »    Full Text »    PDF »
Ligand-dependent folding of the three-way junction in the purine riboswitch.
C. D Stoddard, S. D. Gilbert, and R. T. Batey (2008)
RNA 14, 675-684
   Abstract »    Full Text »    PDF »
Complex Riboswitches.
R. R. Breaker (2008)
Science 319, 1795-1797
   Abstract »    Full Text »    PDF »
Chemical basis of glycine riboswitch cooperativity.
M. Kwon and S. A. Strobel (2008)
RNA 14, 25-34
   Abstract »    Full Text »    PDF »
Mechanism of mRNA destabilization by the glmS ribozyme.
J. A. Collins, I. Irnov, S. Baker, and W. C. Winkler (2007)
Genes & Dev. 21, 3356-3368
   Abstract »    Full Text »    PDF »
Ligand-induced folding of the guanine-sensing riboswitch is controlled by a combined predetermined induced fit mechanism.
O. M. Ottink, S. M. Rampersad, M. Tessari, G. J.R. Zaman, H. A. Heus, and S. S. Wijmenga (2007)
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   Abstract »    Full Text »    PDF »
Guanine riboswitch variants from Mesoplasma florum selectively recognize 2'-deoxyguanosine.
J. N. Kim, A. Roth, and R. R. Breaker (2007)
PNAS 104, 16092-16097
   Abstract »    Full Text »    PDF »
Ligand recognition determinants of guanine riboswitches.
J. Mulhbacher and D. A. Lafontaine (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
A loop loop interaction and a K-turn motif located in the lysine aptamer domain are important for the riboswitch gene regulation control.
S. Blouin and D. A. Lafontaine (2007)
RNA 13, 1256-1267
   Abstract »    Full Text »    PDF »
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Z. Weinberg, J. E. Barrick, Z. Yao, A. Roth, J. N. Kim, J. Gore, J. X. Wang, E. R. Lee, K. F. Block, N. Sudarsan, et al. (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
A noncoding RNA in Saccharomyces cerevisiae is an RNase P substrate.
L. Yang and S. Altman (2007)
RNA 13, 682-690
   Abstract »    Full Text »    PDF »
Ligand binding and gene control characteristics of tandem riboswitches in Bacillus anthracis.
R. Welz and R. R. Breaker (2007)
RNA 13, 573-582
   Abstract »    Full Text »    PDF »
Core requirements of the adenine riboswitch aptamer for ligand binding.
J.-F. Lemay and D. A. Lafontaine (2007)
RNA 13, 339-350
   Abstract »    Full Text »    PDF »
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E. Puerta-Fernandez, J. E. Barrick, A. Roth, and R. R. Breaker (2006)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Tandem Riboswitch Architectures Exhibit Complex Gene Control Functions.
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   Abstract »    Full Text »    PDF »
CMfinder--a covariance model based RNA motif finding algorithm.
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Bioinformatics 22, 445-452
   Abstract »    Full Text »    PDF »
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J. D. Tibodeau, P. M. Fox, P. A. Ropp, E. C. Theil, and H. H. Thorp (2006)
PNAS 103, 253-257
   Abstract »    Full Text »    PDF »
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Cold Spring Harb Symp Quant Biol 71, 239-249
   Abstract »    PDF »
Structural Studies of the Purine and SAM Binding Riboswitches.
Cold Spring Harb Symp Quant Biol 71, 259-268
   Abstract »    PDF »
Sequence-based heuristics for faster annotation of non-coding RNA families.
Z. Weinberg and W. L. Ruzzo (2006)
Bioinformatics 22, 35-39
   Abstract »    Full Text »    PDF »
sinI- and expR-Dependent Quorum Sensing in Sinorhizobium meliloti.
M. Gao, H. Chen, A. Eberhard, M. R. Gronquist, J. B. Robinson, B. G. Rolfe, and W. D. Bauer (2005)
J. Bacteriol. 187, 7931-7944
   Abstract »    Full Text »    PDF »
6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter.
RNA 11, 774-784
   Abstract »    Full Text »    PDF »
Engineered allosteric ribozymes that respond to specific divalent metal ions.
M. Zivarts, Y. Liu, and R. R. Breaker (2005)
Nucleic Acids Res. 33, 622-631
   Abstract »    Full Text »    PDF »
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Science 306, 233-234
   Abstract »    Full Text »    PDF »

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