2009
Engineering ligand-responsive gene-control elements: lessons learned from natural riboswitches
Link K, Breaker R. Engineering ligand-responsive gene-control elements: lessons learned from natural riboswitches. Gene Therapy 2009, 16: 1189-1201. PMID: 19587710, PMCID: PMC5325117, DOI: 10.1038/gt.2009.81.Peer-Reviewed Original Research
2008
In Vitro Selection and Characterization of Cellulose-Binding RNA Aptamers Using isothermal Amplification
Boese B, Corbino K, Breaker R. In Vitro Selection and Characterization of Cellulose-Binding RNA Aptamers Using isothermal Amplification. Nucleosides Nucleotides & Nucleic Acids 2008, 27: 949-966. PMID: 18696364, PMCID: PMC5360192, DOI: 10.1080/15257770802257903.Peer-Reviewed Original ResearchConceptsRNA aptamersRibozyme cleavage productsCellulose affinity chromatographyIsolation of RNARapid amplificationVitro SelectionRibozyme functionRibozyme sequenceFunctional nucleic acidsNucleic acid amplification protocolsRNARobust bindingAffinity chromatographyCleavage productsNucleic acidsSequence replicationBindingSignificant bindingAptamerAmplification protocolAmplification
2005
Gene expression control: Harnessing RNA switches
Breaker R. Gene expression control: Harnessing RNA switches. Gene Therapy 2005, 12: 725-726. PMID: 19202632, DOI: 10.1038/sj.gt.3302461.Peer-Reviewed Original Research
2001
Cooperative binding of effectors by an allosteric ribozyme
Jose A, Soukup G, Breaker R. Cooperative binding of effectors by an allosteric ribozyme. Nucleic Acids Research 2001, 29: 1631-1637. PMID: 11266567, PMCID: PMC31269, DOI: 10.1093/nar/29.7.1631.Peer-Reviewed Original ResearchConceptsAllosteric ribozymesCooperative bindingModular rational designAbsence of effectorsAllosteric proteinsRNA modulesRNA structureMolecular switchAllosteric effectorsFirst bindsFunctional complexityEffectorsDifferent effectorsInduces formationFMNStructural studiesRNARibozymeRibozyme constructsBindingRational designProteinBindsSitesConcertGenerating new ligand-binding RNAs by affinity maturation and disintegration of allosteric ribozymes.
Soukup G, DeRose E, Koizumi M, Breaker R. Generating new ligand-binding RNAs by affinity maturation and disintegration of allosteric ribozymes. RNA 2001, 7: 524-36. PMID: 11345431, PMCID: PMC1370106, DOI: 10.1017/s1355838201002175.Peer-Reviewed Original ResearchConceptsEffector-binding domainAllosteric ribozymesRandom mutagenesisMolecular switchLigand-binding RNAsRNA molecular switchCyclic nucleotide monophosphatesModular rational designSecondary structure organizationSpecific effector moleculesGenetic switchDirect mutational analysisNucleotide covariationsCatalytic domainPhylogeny dataMutational analysisModular engineeringCatalytic moduleNucleic acid structuresNucleotide monophosphatesEffector moleculesAffinity maturationRibozymeMutagenesisHammerhead ribozymeImmobilized RNA switches for the analysis of complex chemical and biological mixtures
Seetharaman S, Zivarts M, Sudarsan N, Breaker R. Immobilized RNA switches for the analysis of complex chemical and biological mixtures. Nature Biotechnology 2001, 19: 336-341. PMID: 11283591, DOI: 10.1038/86723.Peer-Reviewed Original ResearchConceptsDrug analytesMetal ionsBiological mixturesBiosensor arrayAnalyte sensorRNA molecular switchComplex mixturesComplex chemicalMolecular switchEnzyme cofactorMixtureRNA switchesBacterial culture mediumAnalytesMoietyIonsGoldImmobilizationCorresponding effectorsChemicalsStatus of targetAddressable pixelsRibozymeCofactor
2000
Structural diversity of self-cleaving ribozymes
Tang J, Breaker R. Structural diversity of self-cleaving ribozymes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 5784-5789. PMID: 10823936, PMCID: PMC18511, DOI: 10.1073/pnas.97.11.5784.Peer-Reviewed Original ResearchAltering molecular recognition of RNA aptamers by allosteric selection11Edited by D. E. Draper
Soukup G, Emilsson G, Breaker R. Altering molecular recognition of RNA aptamers by allosteric selection11Edited by D. E. Draper. Journal Of Molecular Biology 2000, 298: 623-632. PMID: 10788325, DOI: 10.1006/jmbi.2000.3704.Peer-Reviewed Original ResearchSelection for Catalytic Function with Nucleic Acids
Breaker R. Selection for Catalytic Function with Nucleic Acids. Current Protocols In Nucleic Acid Chemistry 2000, 00: 9.4.1-9.4.17. PMID: 18428882, DOI: 10.1002/0471142700.nc0904s00.Peer-Reviewed Original Research
1999
Nucleic acid molecular switches
Soukup G, Breaker R. Nucleic acid molecular switches. Trends In Biotechnology 1999, 17: 469-476. PMID: 10557159, DOI: 10.1016/s0167-7799(99)01383-9.Peer-Reviewed Original ResearchAllosteric ribozymes sensitive to the second messengers cAMP and cGMP.
Koizumi M, Kerr J, Soukup G, Breaker R. Allosteric ribozymes sensitive to the second messengers cAMP and cGMP. Nucleic Acids Symposium Series 1999, 42: 275-6. PMID: 10780486, DOI: 10.1093/nass/42.1.275.Peer-Reviewed Original ResearchAllosteric selection of ribozymes that respond to the second messengers cGMP and cAMP
Koizumi M, Soukup G, Kerr J, Breaker R. Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP. Nature Structural & Molecular Biology 1999, 6: 1062-1071. PMID: 10542100, DOI: 10.1038/14947.Peer-Reviewed Original ResearchConceptsRNA molecular switchGenetic control elementsMolecular recognition characteristicsEmergence of ribozymesSecond messenger cGMPRNAs exhibitAllosteric ribozymesRNA transcriptsCellular RNASelective sensorCAMP additionMolecular switchFold activationCatalytic rateRecognition characteristicsRibozymeControl elementsEffector compoundsHammerhead ribozymeChemical agentsCompoundsStructural characteristicsSpecific nucleosideNew combinatorial strategyCombinatorial strategiesRelationship between internucleotide linkage geometry and the stability of RNA.
Soukup G, Breaker R. Relationship between internucleotide linkage geometry and the stability of RNA. RNA 1999, 5: 1308-25. PMID: 10573122, PMCID: PMC1369853, DOI: 10.1017/s1355838299990891.Peer-Reviewed Original ResearchDesign of allosteric hammerhead ribozymes activated by ligand-induced structure stabilization
Soukup G, Breaker R. Design of allosteric hammerhead ribozymes activated by ligand-induced structure stabilization. Structure 1999, 7: 783-791. PMID: 10425680, DOI: 10.1016/s0969-2126(99)80102-6.Peer-Reviewed Original ResearchDeoxyribozymes: New players in the ancient game of biocatalysis
Li Y, Breaker R. Deoxyribozymes: New players in the ancient game of biocatalysis. Current Opinion In Structural Biology 1999, 9: 315-323. PMID: 10361095, DOI: 10.1016/s0959-440x(99)80042-6.Peer-Reviewed Original ResearchConceptsSubstrate recognitionGenetic informationIdeal storage systemBiological catalysisRNA counterpartsInert characterChemical reactionsDNANovel chemicalRate enhancementSubstantial untapped potentialNew playersArtificial DNAHelical structurePolynucleotide chainSurprising varietyDeoxyribozymesRecent studiesStructure formationProteinCatalysisBiocatalysisStorage systemReactionChemicalsEngineering precision RNA molecular switches
Soukup G, Breaker R. Engineering precision RNA molecular switches. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 3584-3589. PMID: 10097080, PMCID: PMC22337, DOI: 10.1073/pnas.96.7.3584.Peer-Reviewed Original ResearchConceptsRNA molecular switchMolecular switchGenetic control elementsEnzyme engineering strategiesRNA switchesReceptor domainConformational changesControl elementsEngineering strategiesStructural bridgeModular natureMolecular sensorsStructural reorganizationCorresponding ligandsRNARibozymeSwitchLigandsCatalyticReceptorsTripartite constructsReorganizationDomainIn Vitro Selection of Nucleic Acid Enzymes
Breaker R, Kurz M. In Vitro Selection of Nucleic Acid Enzymes. Current Topics In Microbiology And Immunology 1999, 243: 137-158. PMID: 10453642, DOI: 10.1007/978-3-642-60142-2_8.Peer-Reviewed Original ResearchConceptsDiversity of enzymesYears of evolutionNucleic acid enzymesEvolutionary historyNucleic acidsBiochemical functionsDNA substratesMetabolic machineryVitro SelectionProtein enzymesCatalytic functionBiological catalystsAcid enzymesHydrolysis reactionProteinEnzymeNatural functionRibozymeDistinct classesRNAEssential componentReactionMachineryCatalystDiversity
1998
Mechanism for allosteric inhibition of an ATP-sensitive ribozyme
Tang J, Breaker R. Mechanism for allosteric inhibition of an ATP-sensitive ribozyme. Nucleic Acids Research 1998, 26: 4214-4221. PMID: 9722642, PMCID: PMC147823, DOI: 10.1093/nar/26.18.4214.Peer-Reviewed Original ResearchConceptsAllosteric ribozymesModular rational designFunctional modulationEffector moleculesSelf-cleaving ribozymesFunction of ribozymesSmall effector moleculesPresence of ATPAbsence of ATPAptamer domainStructural basisLigand bindingAllosteric inhibitionRibozyme domainPossible mechanismTertiary structureConformational changesRibozymeAn amino acid as a cofactor for a catalytic polynucleotide
Roth A, Breaker R. An amino acid as a cofactor for a catalytic polynucleotide. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 6027-6031. PMID: 9600911, PMCID: PMC27579, DOI: 10.1073/pnas.95.11.6027.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsBase SequenceDNA, Single-StrandedHistidineMolecular Sequence DataPolynucleotidesRNA, CatalyticConceptsAmino acidsRate enhancementDramatic rate enhancementMetal ion cofactorsAbsence of enzymeGeneral base catalystSuperior polymerChemical catalysisBiological catalystsRNA cleavage reactionCatalytic potentialOrganic cofactorImidazole groupsNatural ribozymesRNA worldBase catalystChemical groupsCatalytic mechanismCatalytic DNACleavage reactionIon cofactorProtein enzymesStructural foldingSubstrate cleavageConstituent amino acids
1997
Examination of the catalytic fitness of the hammerhead ribozyme by in vitro selection.
Tang J, Breaker R. Examination of the catalytic fitness of the hammerhead ribozyme by in vitro selection. RNA 1997, 3: 914-25. PMID: 9257650, PMCID: PMC1369536.Peer-Reviewed Original ResearchConceptsConsensus sequenceATP-binding RNA aptamerCatalytic fitnessHammerhead ribozymeAbsence of ATPRNA poolAllosteric ribozymesVitro SelectionRNA aptamersCatalytic functionSequence variantsAllosteric interactionsCombinatorial poolsRibozymeTranscriptionATPRNACatalytic rateSequenceHammerhead domainRibozyme constructsFitnessAllosteric delayPoolSimilar strategies