Ronald Breaker

Summary

Affiliation: Yale University
Country: USA

Publications

  1. pmc Identification of a large noncoding RNA in extremophilic eubacteria
    Elena Puerta-Fernandez
    Department of Molecular, Yale University, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 103:19490-5. 2006
  2. pmc Riboswitches that sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling
    Joy Xin Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Mol Cell 29:691-702. 2008
  3. pmc New insight on the response of bacteria to fluoride
    R R Breaker
    Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, Box 208103 New Haven, CT 06520 8103, USA
    Caries Res 46:78-81. 2012
  4. pmc The distributions, mechanisms, and structures of metabolite-binding riboswitches
    Jeffrey E Barrick
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8103, USA
    Genome Biol 8:R239. 2007
  5. pmc Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes
    Zasha Weinberg
    Howard Hughes Medical Institute, Yale University, New Haven, CT 06520 8103, USA
    Genome Biol 11:R31. 2010
  6. pmc Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria
    Keith A Corbino
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Genome Biol 6:R70. 2005
  7. pmc Identification of candidate structured RNAs in the marine organism 'Candidatus Pelagibacter ubique'
    Michelle M Meyer
    Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    BMC Genomics 10:268. 2009
  8. pmc R2R--software to speed the depiction of aesthetic consensus RNA secondary structures
    Zasha Weinberg
    Howard Hughes Medical Institute, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    BMC Bioinformatics 12:3. 2011
  9. doi request reprint RNA switches out in the cold
    Ronald R Breaker
    Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Mol Cell 37:1-2. 2010
  10. doi request reprint Complex riboswitches
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology and Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA
    Science 319:1795-7. 2008

Research Grants

  1. ENGINEERING ALLOSTERIC RIBOZYMES AND DEOXYRIBOZYMES
    Ronald Breaker; Fiscal Year: 2002
  2. Natural mRNA Genetic Switches that Bind Metabolites
    Ronald Breaker; Fiscal Year: 2006
  3. Measuring Metabolites using Riboswitch reports
    Ronald Breaker; Fiscal Year: 2006

Collaborators

Detail Information

Publications80

  1. pmc Identification of a large noncoding RNA in extremophilic eubacteria
    Elena Puerta-Fernandez
    Department of Molecular, Yale University, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 103:19490-5. 2006
    ..The patterns of structural conservation, and its unique phylogenetic distribution, suggest that OLE RNA carries out a complex and critical function only in certain extremophilic bacteria...
  2. pmc Riboswitches that sense S-adenosylhomocysteine and activate genes involved in coenzyme recycling
    Joy Xin Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Mol Cell 29:691-702. 2008
    ..These observations confirm that SAH motif RNAs are distinct ligand-binding aptamers for a riboswitch class that selectively binds SAH and controls genes essential for recycling expended SAM coenzymes...
  3. pmc New insight on the response of bacteria to fluoride
    R R Breaker
    Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, Yale University, Box 208103 New Haven, CT 06520 8103, USA
    Caries Res 46:78-81. 2012
    ..Below I provide a summary of our findings, comment on some of the key prospects for expanding our understanding of fluoride's effects on biology, and propose some future uses of this knowledge...
  4. pmc The distributions, mechanisms, and structures of metabolite-binding riboswitches
    Jeffrey E Barrick
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8103, USA
    Genome Biol 8:R239. 2007
    ....
  5. pmc Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes
    Zasha Weinberg
    Howard Hughes Medical Institute, Yale University, New Haven, CT 06520 8103, USA
    Genome Biol 11:R31. 2010
    ..Structured RNAs can be detected by comparative genomics, in which homologous sequences are identified and inspected for mutations that conserve RNA secondary structure...
  6. pmc Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria
    Keith A Corbino
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Genome Biol 6:R70. 2005
    ..Riboswitches are most common in the genomes of low GC Gram-positive bacteria (for example, Bacillus subtilis contains examples of all known riboswitches), and some riboswitch classes seem to be restricted to this group...
  7. pmc Identification of candidate structured RNAs in the marine organism 'Candidatus Pelagibacter ubique'
    Michelle M Meyer
    Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    BMC Genomics 10:268. 2009
    ..The genome of 'Candidatus Pelagibacter ubique' HTCC 1062 is the closest match for approximately 20% of marine metagenomic sequence reads. It is also small, contains little non-coding DNA, and has strikingly low GC content...
  8. pmc R2R--software to speed the depiction of aesthetic consensus RNA secondary structures
    Zasha Weinberg
    Howard Hughes Medical Institute, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    BMC Bioinformatics 12:3. 2011
    ..Additionally, most existing RNA-specific applications are designed for drawing single RNA molecules, not consensus diagrams...
  9. doi request reprint RNA switches out in the cold
    Ronald R Breaker
    Howard Hughes Medical Institute, Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Mol Cell 37:1-2. 2010
    ..In this issue of Molecular Cell, Giuliodori et al. (2010) describe a cold-induced genetic switch made of RNA. Could thermo-sensing RNAs be among the most common types of RNA genetic switches?..
  10. doi request reprint Complex riboswitches
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology and Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA
    Science 319:1795-7. 2008
    ..Although modern riboswitches might be the last holdouts of primitive genetic elements, some are capable of sensory and regulatory feats that are competitive with their protein counterparts...
  11. ncbi request reprint DNA enzymes
    R R Breaker
    Department of Biology, Yale University, New Haven, CT 06520 8103, USA
    Nat Biotechnol 15:427-31. 1997
    ..An assessment of the potential for structure formation by DNA leads to the conclusion that DNA might have considerable latent potential for enzymatic function...
  12. doi request reprint Prospects for riboswitch discovery and analysis
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Mol Cell 43:867-79. 2011
    ..Some of the greatest prospects for riboswitch research and some of the more interesting mysteries are discussed in this review...
  13. pmc A common speed limit for RNA-cleaving ribozymes and deoxyribozymes
    Ronald R Breaker
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 9:949-57. 2003
    ..These results indicate that ribozymes using additional catalytic strategies could be made that promote RNA cleavage with rate enhancements that equal those of proteins...
  14. ncbi request reprint Natural and engineered nucleic acids as tools to explore biology
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520 8103, USA
    Nature 432:838-45. 2004
    ..Molecular engineers are beginning to harness the power of nucleic acids that form more complex three-dimensional structures, and apply them as tools for exploring biological systems and as therapeutics...
  15. ncbi request reprint DNA aptamers and DNA enzymes
    R R Breaker
    Department of Biology, KBT 452, Yale University, PO Box 208103, New Haven, CT 06520, USA
    Curr Opin Chem Biol 1:26-31. 1997
    ....
  16. ncbi request reprint Engineered allosteric ribozymes as biosensor components
    Ronald R Breaker
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Curr Opin Biotechnol 13:31-9. 2002
    ..Engineered molecular switches can be used to report the presence of specific analytes in complex mixtures, making possible the creation of new types of biosensor devices and genetic control elements...
  17. ncbi request reprint Are engineered proteins getting competition from RNA?
    R R Breaker
    Department of Biology, Yale University, New Haven, CT 06520, USA
    Curr Opin Biotechnol 7:442-8. 1996
    ..Some engineered RNAs offer potential as therapeutic agents whereas others can be used as model systems to study the principles that direct structure formation, molecular recognition and catalytic function by nucleic acids...
  18. pmc Coenzyme B12 riboswitches are widespread genetic control elements in prokaryotes
    Ali Nahvi
    Department of Molecular Biophysics and Biochemistry, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    Nucleic Acids Res 32:143-50. 2004
    ....
  19. ncbi request reprint Engineering high-speed allosteric hammerhead ribozymes
    Kristian H Link
    Howard Hughes Medical Institute, Yale University, New Haven, CT 06520 8103, USA
    Biol Chem 388:779-86. 2007
    ..These results provide several key pieces of information that will aid in future efforts to engineer allosteric ribozymes for gene control applications...
  20. ncbi request reprint The kinetics of ligand binding by an adenine-sensing riboswitch
    J Kenneth Wickiser
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 8103, USA
    Biochemistry 44:13404-14. 2005
    ....
  21. ncbi request reprint Adenine riboswitches and gene activation by disruption of a transcription terminator
    Maumita Mandal
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nat Struct Mol Biol 11:29-35. 2004
    ....
  22. doi request reprint Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis
    Zasha Weinberg
    Howard Hughes Medical Institute, New Haven, Connecticut 06520 8103, USA
    Nature 462:656-9. 2009
    ....
  23. pmc A plant 5S ribosomal RNA mimic regulates alternative splicing of transcription factor IIIA pre-mRNAs
    Ming C Hammond
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 16:541-9. 2009
    ..This study also provides insight into the origin and function of a newfound class of structured RNA that regulates alternative splicing...
  24. ncbi request reprint Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes
    Robert Penchovsky
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nat Biotechnol 23:1424-33. 2005
    ..This engineering approach provides a rapid and inexpensive way to create allosteric RNAs for constructing complex molecular circuits, nucleic acid detection systems and gene control elements...
  25. ncbi request reprint A glycine-dependent riboswitch that uses cooperative binding to control gene expression
    Maumita Mandal
    Department of Molecular, Cellular, and Developmental Biology, Yale University, Post Office Box 208103, New Haven, CT 06520 8103, USA
    Science 306:275-9. 2004
    ..Thus, riboswitches perform key regulatory roles and exhibit complex performance characteristics that previously had been observed only with protein factors...
  26. pmc Riboswitch control of gene expression in plants by splicing and alternative 3' end processing of mRNAs
    Andreas Wachter
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Conecticut 06520, USA
    Plant Cell 19:3437-50. 2007
    ..These findings highlight the importance of metabolite sensing by riboswitches in plants and further reveal the significance of alternative 3' end processing as a mechanism of gene control in eukaryotes...
  27. pmc A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism
    Elizabeth E Regulski
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Mol Microbiol 68:918-32. 2008
    ..Furthermore, we identify variants of this RNA that are likely to be triggered by the related tungsten cofactor (Tuco), which carries tungsten in place of molybdenum as the metal constituent...
  28. pmc Ligand binding and gene control characteristics of tandem riboswitches in Bacillus anthracis
    Rüdiger Welz
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    RNA 13:573-82. 2007
    ..Our findings further demonstrate that simple gene control elements made only of RNA can be assembled in different architectures to yield more complex gene control outcomes...
  29. ncbi request reprint Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression
    Wade Winkler
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nature 419:952-6. 2002
    ..This metabolite-sensing regulatory system provides an example of a 'riboswitch' whose evolutionary origin might pre-date the emergence of proteins...
  30. pmc 6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter
    Jeffrey E Barrick
    Department of Molecular, Cellular, and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520, USA
    RNA 11:774-84. 2005
    ..coli ygfA gene encoding a putative methenyltetrahydrofolate synthetase. The prevalence and robust expression of 6S RNAs emphasize their critical role in bacterial adaptation...
  31. ncbi request reprint Riboswitches as antibacterial drug targets
    Kenneth F Blount
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, Connecticut 06520, USA
    Nat Biotechnol 24:1558-64. 2006
    ..Herein we will summarize the experiments validating riboswitches as drug targets, describe the existing technology for riboswitch drug discovery and discuss the challenges that may face riboswitch drug discoverers...
  32. ncbi request reprint The power of riboswitches
    Jeffrey E Barrick
    Breaker s Laboratory, Yale University, USA
    Sci Am 296:50-7. 2007
  33. ncbi request reprint A riboswitch selective for the queuosine precursor preQ1 contains an unusually small aptamer domain
    Adam Roth
    Howard Hughes Medical Institute, USA
    Nat Struct Mol Biol 14:308-17. 2007
    ..Relatively compact RNA structures can therefore serve effectively as metabolite receptors to regulate gene expression...
  34. pmc Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline
    Zasha Weinberg
    Department of Molecular, Cellular and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    Nucleic Acids Res 35:4809-19. 2007
    ..These candidate RNAs add to the growing list of RNA motifs involved in multiple cellular processes, and suggest that many additional RNAs remain to be discovered...
  35. ncbi request reprint An mRNA structure that controls gene expression by binding S-adenosylmethionine
    Wade C Winkler
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nat Struct Biol 10:701-7. 2003
    ..This and related findings indicate that direct interaction between small metabolites and allosteric mRNAs is an important and widespread form of genetic regulation in bacteria...
  36. pmc The aptamer core of SAM-IV riboswitches mimics the ligand-binding site of SAM-I riboswitches
    Zasha Weinberg
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 14:822-8. 2008
    ..Our findings support the view that RNA has considerable structural versatility and reveal that riboswitches exploit this potential to expand the scope of RNA in genetic regulation...
  37. doi request reprint In-line probing analysis of riboswitches
    Elizabeth E Regulski
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, USA
    Methods Mol Biol 419:53-67. 2008
    ..Although this method has most frequently been used to examine riboswitches, the structures of any RNAs can be examined using this technique...
  38. pmc Substrate specificity and reaction kinetics of an X-motif ribozyme
    Denis Lazarev
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    RNA 9:688-97. 2003
    ..The ribozyme has an absolute requirement for a divalent cation cofactor and exhibits kinetic behavior that is consistent with the obligate binding of at least two metal ions...
  39. pmc Confirmation of a second natural preQ1 aptamer class in Streptococcaceae bacteria
    Michelle M Meyer
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 14:685-95. 2008
    ..Additionally, the association of preQ(1) binding RNAs with most genes encoding proteins classified as COG4708 strongly suggests that these proteins function as transporters for preQ(1) or another queuosine biosynthetic intermediate...
  40. ncbi request reprint Genetic control by a metabolite binding mRNA
    Ali Nahvi
    Department of Molecular Biophysics and Biochemistry, P O Box 208114, New Haven, CT 06520, USA
    Chem Biol 9:1043. 2002
    ..This finding, along with related observations, supports the hypothesis that metabolic monitoring through RNA-metabolite interactions is a widespread mechanism of genetic control...
  41. ncbi request reprint Antibacterial lysine analogs that target lysine riboswitches
    Kenneth F Blount
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, KBT 506, New Haven, Connecticut 06520, USA
    Nat Chem Biol 3:44-9. 2007
    ..These results indicate that riboswitches could serve as new classes of antibacterial drug targets...
  42. doi request reprint The structural and functional diversity of metabolite-binding riboswitches
    Adam Roth
    Howard Hughes Medical Institute, Yale University, New Haven, CT 06520 8103, USA
    Annu Rev Biochem 78:305-34. 2009
    ..This diverse set of metabolite-sensing RNAs is found to exploit a variety of distinct mechanisms to regulate genes that are fundamental to metabolism...
  43. ncbi request reprint Tandem riboswitch architectures exhibit complex gene control functions
    Narasimhan Sudarsan
    Department of Molecular, Cellular and Developmental Biology, Yale University, Post Office Box 208103, New Haven, CT 06520 8103, USA
    Science 314:300-4. 2006
    ..These findings and the discovery of additional tandem riboswitch architectures reveal how simple RNA elements can be assembled to make sophisticated genetic decisions without involving protein factors...
  44. doi request reprint An allosteric self-splicing ribozyme triggered by a bacterial second messenger
    Elaine R Lee
    Department of Molecular, Cellular, and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    Science 329:845-8. 2010
    ..Our findings indicate that some self-splicing ribozymes are not selfish elements but are harnessed by cells as metabolite sensors and genetic regulators...
  45. doi request reprint In vitro selection of glmS ribozymes
    Kristian H Link
    Yale University, New Haven, CT 06520 8103, USA
    Methods Mol Biol 540:349-64. 2009
    ..In this chapter, we describe how in vitro selection can be used to create variant glmS ribozymes. Additionally, we discuss how these techniques can be extended to other riboswitch classes...
  46. ncbi request reprint Gene regulation by riboswitches
    Maumita Mandal
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520 8103, USA
    Nat Rev Mol Cell Biol 5:451-63. 2004
  47. ncbi request reprint Selection in vitro of allosteric ribozymes
    Adam Roth
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA
    Methods Mol Biol 252:145-64. 2004
    ....
  48. pmc Structural basis of ligand binding by a c-di-GMP riboswitch
    Kathryn D Smith
    Department of Chemistry, Yale University, New Haven, Connecticut, USA
    Nat Struct Mol Biol 16:1218-23. 2009
    ....
  49. pmc A eubacterial riboswitch class that senses the coenzyme tetrahydrofolate
    Tyler D Ames
    Department of Molecular, Cellular and Developmental Biology, Yale University, Box 208103, New Haven, CT 06520 8103, USA
    Chem Biol 17:681-5. 2010
    ..These findings expand the number of coenzymes that are directly sensed by RNA and reveal possible riboswitch-controlled regulons that respond to changes in single-carbon metabolism...
  50. ncbi request reprint Development and application of a high-throughput assay for glmS riboswitch activators
    Kenneth Blount
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    RNA Biol 3:77-81. 2006
    ..These results demonstrate that modern high-throughput screening techniques can be applied to the discovery of riboswitch-targeted drug compounds...
  51. pmc An mRNA structure that controls gene expression by binding FMN
    Wade C Winkler
    Department of Molecular, Cellular, and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 99:15908-13. 2002
    ..Sequence and structural analyses indicate that the RFN element is a natural FMN-binding aptamer, the allosteric character of which is harnessed to control gene expression...
  52. pmc Evidence for widespread gene control function by the ydaO riboswitch candidate
    Kirsten F Block
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    J Bacteriol 192:3983-9. 2010
    ..The mutations disrupt genes that drastically modulate energy-generating pathways, suggesting that the intracellular concentration of the ligand sensed by the ydaO motif is altered under these stress conditions...
  53. ncbi request reprint Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression
    Elaine R Lee
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    RNA Biol 6:187-94. 2009
    ..If FMN riboswitches are a major target for roseoflavin antimicrobial action, then future efforts to develop compounds that trigger FMN riboswitch function could lead to the identification of new antimicrobial drugs...
  54. doi request reprint Design and antimicrobial action of purine analogues that bind Guanine riboswitches
    Jane N Kim
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520 8103, USA
    ACS Chem Biol 4:915-27. 2009
    ..This approach also could be implemented to design antibacterial compounds that specifically target other riboswitch classes...
  55. ncbi request reprint Genetic control by metabolite-binding riboswitches
    Wade C Winkler
    Department of Molecular, Cellular, and Developmental Biology, Yale University, Kline Biology Tower 506, 266 Whitney Avenue, New Haven, CT 06520, USA
    Chembiochem 4:1024-32. 2003
  56. pmc A variant riboswitch aptamer class for S-adenosylmethionine common in marine bacteria
    Elena Poiata
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    RNA 15:2046-56. 2009
    ..This tandem riboswitch arrangement exhibits an architecture that can potentially control both the transcriptional and translational stages of gene expression...
  57. ncbi request reprint Characteristics of ligand recognition by a glmS self-cleaving ribozyme
    Jinsoo Lim
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Angew Chem Int Ed Engl 45:6689-93. 2006
  58. pmc Importance of the Debye screening length on nanowire field effect transistor sensors
    Eric Stern
    Department of Biomedical Engineering, Yale University, PO Box 208284, New Haven, Connecticut 06520, USA
    Nano Lett 7:3405-9. 2007
    ..Here we show the appropriate conditions under which the selective binding of macromolecules is accurately sensed with NW-FET sensors...
  59. doi request reprint Riboswitches that sense S-adenosylmethionine and S-adenosylhomocysteine
    Joy Xin Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
    Biochem Cell Biol 86:157-68. 2008
    ....
  60. pmc Ribozyme speed limits
    Gail Mitchell Emilsson
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 9:907-18. 2003
    ..We deduce that certain ribozymes and deoxyribozymes, like their protein enzyme counterparts, can bring about enormous rate enhancements...
  61. ncbi request reprint The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch
    J Kenneth Wickiser
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
    Mol Cell 18:49-60. 2005
    ..quot; This reliance on the kinetics of ligand association and RNA polymerization speed might be common for riboswitches that utilize transcription termination mechanisms...
  62. pmc Engineered allosteric ribozymes that respond to specific divalent metal ions
    Maris Zivarts
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    Nucleic Acids Res 33:622-31. 2005
    ..Additional findings suggest that, although complex allosteric functions can be exhibited by small RNAs, larger RNA molecules will probably be required to form binding pockets that are uniquely selective for individual cation effectors...
  63. ncbi request reprint Molecular-recognition characteristics of SAM-binding riboswitches
    Jinsoo Lim
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Angew Chem Int Ed Engl 45:964-8. 2006
  64. pmc Characteristics of the glmS ribozyme suggest only structural roles for divalent metal ions
    Adam Roth
    Howard Hughes Medical Institute, Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520 8103, USA
    RNA 12:607-19. 2006
    ..Our findings indicate that the glmS ribozyme forms a complex structure to employ catalytic strategies that do not require the direct participation of divalent metal ions...
  65. pmc New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control
    Jeffrey E Barrick
    Department of Molecular Biophysics and Biochemistry, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 101:6421-6. 2004
    ..These findings indicate that riboswitches serve as a major genetic regulatory mechanism for the control of metabolic genes in many microbial species...
  66. pmc In vitro selection and characterization of cellulose-binding DNA aptamers
    Benjamin J Boese
    Department of Chemical Engineering, Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Nucleic Acids Res 35:6378-88. 2007
    ..CELAPT 14 aptamer variants exhibit robust binding both to cellulose powder and paper. Also, an allosteric aptamer construct was engineered that exhibits ATP-mediated cellulose binding during paper chromatography...
  67. ncbi request reprint Control of gene expression by a natural metabolite-responsive ribozyme
    Wade C Winkler
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nature 428:281-6. 2004
    ..These findings demonstrate that ribozyme switches may have functioned as metabolite sensors in primitive organisms, and further suggest that modern cells retain some of these ancient genetic control systems...
  68. ncbi request reprint Ligating DNA with DNA
    Alavattam Sreedhara
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    J Am Chem Soc 126:3454-60. 2004
    ..However, the sequence requirements of the AppDNA and that of the 3' terminus of the deoxyribozyme ligase limit the range of sequences that can be ligated...
  69. pmc Guanine riboswitch variants from Mesoplasma florum selectively recognize 2'-deoxyguanosine
    Jane N Kim
    Department of Molecular, Cellular, and Developmental Biology, Yale University, PO Box 208103, New Haven, CT 06520 8103, USA
    Proc Natl Acad Sci U S A 104:16092-7. 2007
    ..The identification of riboswitch variants that bind nucleosides and reject nucleobases reveals that natural metabolite-sensing RNA motifs can accrue mutations that expand the diversity of ligand detection in bacteria...
  70. ncbi request reprint Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs
    Alexander Serganov
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Chem Biol 11:1729-41. 2004
    ..Recognition specificity is associated with Watson-Crick pairing of the encapsulated adenine and guanine ligands with uridine and cytosine, respectively...
  71. ncbi request reprint Purine sensing by riboswitches
    Jane N Kim
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, CT 06520 8103, USA
    Biol Cell 100:1-11. 2008
    ..This review will provide a summary of the purine-sensing riboswitches, as well as discuss the complex functions and applications of these RNAs...
  72. pmc Metabolite-binding RNA domains are present in the genes of eukaryotes
    Narasimhan Sudarsan
    RNA 9:644-7. 2003
    ..These results suggest that metabolite-binding mRNAs are possibly involved in eukaryotic gene regulation and that some riboswitches might be representatives of an ancient form of genetic control...
  73. ncbi request reprint Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch
    Alexander Serganov
    Nature 441:1167-71. 2006
    ..In addition, this structure provides insight into how folded RNAs can form precision binding pockets that rival those formed by protein genetic factors...
  74. ncbi request reprint Regulation of bacterial gene expression by riboswitches
    Wade C Winkler
    Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Annu Rev Microbiol 59:487-517. 2005
    ..Numerous classes of riboswitches are present in bacteria and they comprise a common and robust metabolite-sensing system...
  75. ncbi request reprint Riboswitches as versatile gene control elements
    Brian J Tucker
    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA
    Curr Opin Struct Biol 15:342-8. 2005
    ....
  76. pmc Examination of the structural and functional versatility of glmS ribozymes by using in vitro selection
    Kristian H Link
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Nucleic Acids Res 34:4968-75. 2006
    ..These findings are consistent with the hypothesis that GlcN6P is used by the ribozyme as a coenzyme for RNA cleavage, rather than an allosteric effector...
  77. ncbi request reprint Control of alternative RNA splicing and gene expression by eukaryotic riboswitches
    Ming T Cheah
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA
    Nature 447:497-500. 2007
    ..These results demonstrate that eukaryotic cells employ metabolite-binding RNAs to regulate RNA splicing events that are important for the control of key biochemical processes...
  78. pmc An mRNA structure in bacteria that controls gene expression by binding lysine
    Narasimhan Sudarsan
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    Genes Dev 17:2688-97. 2003
    ..These findings add support to the hypotheses that direct sensing of metabolites by messenger RNAs is a fundamental form of genetic control and that riboswitches represent a new class of antimicrobial drug targets...
  79. ncbi request reprint Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria
    Maumita Mandal
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Cell 113:577-86. 2003
    ..Furthermore, it is now apparent that riboswitches contribute to the regulation of numerous fundamental metabolic pathways in certain bacteria...
  80. ncbi request reprint Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine
    Narasimhan Sudarsan
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520, USA
    Chem Biol 12:1325-35. 2005
    ..Our findings demonstrate that riboswitches can serve as antimicrobial drug targets and expand our understanding of thiamine metabolism in bacteria...

Research Grants9

  1. ENGINEERING ALLOSTERIC RIBOZYMES AND DEOXYRIBOZYMES
    Ronald Breaker; Fiscal Year: 2002
    ..In addition, we will test the function of these 'molecular switches' in vivo, to establish a new method of controlled gene expression. ..
  2. Natural mRNA Genetic Switches that Bind Metabolites
    Ronald Breaker; Fiscal Year: 2006
    ..These findings will aid in the discovery of new riboswitches and will provide a solid foundation for the generation of designer genetic control elements based on RNA. ..
  3. Measuring Metabolites using Riboswitch reports
    Ronald Breaker; Fiscal Year: 2006
    ..Moreover, bioinformatics searches can be expanded to uncover examples of known or new riboswitches in humans and other eukaryotes. ..