Featured Publications
Discovering riboswitches: the past and the future
Kavita K, Breaker RR. Discovering riboswitches: the past and the future. Trends In Biochemical Sciences 2022, 48: 119-141. PMID: 36150954, PMCID: PMC10043782, DOI: 10.1016/j.tibs.2022.08.009.Peer-Reviewed Original Research
2024
Prospects for Riboswitches in Drug Development
Mohsen M, Breaker R. Prospects for Riboswitches in Drug Development. Methods And Principles In Medicinal Chemistry 2024, 203-226. DOI: 10.1002/9783527840458.ch8.Peer-Reviewed Original ResearchUntranslated regions of messenger RNAsRegions of messenger RNAsModulate gene expressionBacterial physiologyEngineered riboswitchesSynthetic switchesRNA structureRiboswitch functionRiboswitchUntranslated regionSmall moleculesDrug developmentGene expressionDrug-like small moleculesHuman gene therapy applicationsMessenger RNARNAGene therapy applicationsAntibiotic agentsTargeting ligandsTherapy applicationsProteinMoleculesDrugEngineered Branaplam Aptamers Exploit Structural Elements from Natural Riboswitches
Mohsen M, Midy M, Balaji A, Breaker R. Engineered Branaplam Aptamers Exploit Structural Elements from Natural Riboswitches. ACS Chemical Biology 2024, 19: 1447-1452. PMID: 38954594, PMCID: PMC11267568, DOI: 10.1021/acschembio.4c00358.Peer-Reviewed Original ResearchRNA poolRiboswitch aptamerAptamer candidatesPaired elementsIn vitro selectionNatural riboswitchesHuntington's diseaseThiamine pyrophosphateAptamer developmentRiboswitchDrug candidatesAptamerStructural scaffoldBranaplamRNASpinal muscular atrophyImproved bindingTreat spinal muscular atrophySmall moleculesBioavailability characteristicsDissociation constantPseudoknotMuscular atrophyStructural elementsPool
2023
8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage
Dhakal S, Kavita K, Panchapakesan S, Roth A, Breaker R. 8-oxoguanine riboswitches in bacteria detect and respond to oxidative DNA damage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2307854120. PMID: 37748066, PMCID: PMC10556655, DOI: 10.1073/pnas.2307854120.Peer-Reviewed Original ResearchConceptsAptamer domainGene expressionLigand specificityOxidative damageLigand-binding pocketRiboswitch classesFamilies of bacteriaRare variantsRiboswitch aptamerCertain oxidative stressesExposure of cellsOxidative DNA damageRiboswitchGene associationsRNA aptamersDNA damageNucleotide poolBacteriaTarget ligandsOxidative stressMutationsNumerous alterationsPurine derivativesExpressionVariantsIn vitro Selection and in vivo Testing of Riboswitch-inspired Aptamers
Mohsen M, Breaker R. In vitro Selection and in vivo Testing of Riboswitch-inspired Aptamers. Bio-protocol 2023, 13: e4775. PMID: 37456339, PMCID: PMC10338711, DOI: 10.21769/bioprotoc.4775.Peer-Reviewed Original ResearchAptamer candidatesSubsequent biochemical validationComplex cellular environmentVitro selection protocolSelfish sequencesRiboswitch aptamerNext-generation sequencingRNA poolBacterial cell cultureExpression platformCellular environmentBacterial cellsBiochemical validationStructural scaffoldLigand candidatesCell culturesSelection protocolAptamerRiboswitchNew ligandsSelectionBioinformaticsSequencingScaffold typesSequenceRiboswitches
Salvail H, Breaker R. Riboswitches. Current Biology 2023, 33: r343-r348. PMID: 37160088, PMCID: PMC11207198, DOI: 10.1016/j.cub.2023.03.069.Peer-Reviewed Original ResearchScreening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch
Sadeeshkumar H, Balaji A, Sutherland A, Mootien S, Anthony K, Breaker R. Screening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch. Analytical Biochemistry 2023, 666: 115047. PMID: 36682579, PMCID: PMC11149561, DOI: 10.1016/j.ab.2023.115047.Peer-Reviewed Original ResearchConceptsHigh-throughput screenAutoinducer-2Reporter geneBacterial processesEssential bacterial processesGram-negative bacterial cellsQuorum sensing signalsΒ-galactosidase reporter geneSmall molecule inhibitorsAntibiotic drug discoveryNatural riboswitchesAntimicrobial drug developmentRNA elementsPhysiological signalingRiboswitchBacterial cellsMolecule inhibitorsS-adenosylmethionineEscherichia coliCritical functionsNew targetsGenesDrug discoverySmall moleculesPromising targetExploiting natural riboswitches for aptamer engineering and validation
Mohsen M, Midy M, Balaji A, Breaker R. Exploiting natural riboswitches for aptamer engineering and validation. Nucleic Acids Research 2023, 51: 966-981. PMID: 36617976, PMCID: PMC9881172, DOI: 10.1093/nar/gkac1218.Peer-Reviewed Original ResearchConceptsNatural riboswitchesRiboswitch aptamerReporter gene expressionSecondary structure featuresRNA poolExpression platformVivo functionGene expressionSurvival mechanismRNA sequencesStructural featuresRiboswitchAptamer selectionSmall moleculesSequenceAptamerCellsGuanineTest tubeFuture effortsSelectionSelection strategyExpressionPoolAptamer engineering
2022
Lithium-sensing riboswitch classes regulate expression of bacterial cation transporter genes
White N, Sadeeshkumar H, Sun A, Sudarsan N, Breaker R. Lithium-sensing riboswitch classes regulate expression of bacterial cation transporter genes. Scientific Reports 2022, 12: 19145. PMID: 36352003, PMCID: PMC9646797, DOI: 10.1038/s41598-022-20695-6.Peer-Reviewed Original Research
2019
Genome‐wide Discovery of Rare Riboswitches in Bacteria
Arachchilage G, Atilho R, Stav S, Higgs G, Breaker R. Genome‐wide Discovery of Rare Riboswitches in Bacteria. The FASEB Journal 2019, 33: 778.8-778.8. DOI: 10.1096/fasebj.2019.33.1_supplement.778.8.Peer-Reviewed Original ResearchRiboswitch candidatesBacterial genomesGC-rich intergenic regionsDifferent bacterial genomesGenome-wide discoverySequenced bacterial genomesNascent RNA transcriptsRiboswitch classesThiamin biosynthesisRiboswitch aptamerStructured ncRNAsNcRNA classesIntergenic regionHydroxymethylpyrimidine pyrophosphateRiboswitchBioinformatics pipelineRNA transcriptsTranscription processComputational pipelinePhysiological pathwaysConformational changesNcRNAsGenomeFASEB JournalHoward Hughes Medical Institute
2018
High Throughput Validation of Orphan Riboswitch Candidates
Arachchilage G, Sherlock M, White N, Panchapakesan S, Breaker R. High Throughput Validation of Orphan Riboswitch Candidates. The FASEB Journal 2018, 32: lb18-lb18. DOI: 10.1096/fasebj.2018.32.1_supplement.lb18.Peer-Reviewed Original ResearchRiboswitch candidatesRiboswitch classesIntergenic regionCognate ligandsS-adenosylmethionineLong intergenic regionCis-acting genesDiscovery of riboswitchesExperimental Biology 2018 MeetingImportant biological pathwaysHigh-throughput validationHigh-throughput strategyS-adenosylhomocysteineComparative genomicsRecent bioinformaticsBacterial mRNAsLine probingRNA elementsRiboswitchGenetic validationReporter assaysBiological pathwaysComputational approachThroughput strategyFASEB Journal
2016
Prospects for Noncoding RNA Discovery in Bacteria
Breaker R. Prospects for Noncoding RNA Discovery in Bacteria. The FASEB Journal 2016, 30 DOI: 10.1096/fasebj.30.1_supplement.386.1.Peer-Reviewed Original ResearchNoncoding RNAsNovel biochemical functionLarge noncoding RNAsBacterial noncoding RNAsRNA world organismsSelf-cleaving ribozymesRiboswitch candidatesRNA discoveryBiological validation studiesBiochemical functionsBioinformatics analysisModern cellsWorld organismsRNAGreat diversityStructural diversityNovel ribozymesRibozymeDiversityBacteriaDiscoveryRiboswitchRNAsOrganismsCells
2010
Riboswitches That Sense Cyclic Di‐GMP
Lee E, Sudarsan N, Breaker R. Riboswitches That Sense Cyclic Di‐GMP. 2010, 215-229. DOI: 10.1128/9781555816667.ch15.Peer-Reviewed Original ResearchGMP riboswitchSecond messengerUntranslated regionCyclic di-GMPHigh sequence conservationAssociation of genesSecond messenger signalingSecondary structure elementsEntire regulonDifferent genetic backgroundsTranscription elongationSequence conservationRNA functionTranslation initiationLine probingDifferent environmental conditionsRiboswitchRegulatory ligandsProtein productsNew hostGenesMessenger RNAGenetic backgroundGreat diversityEnvironmental conditions
2008
Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP
Sudarsan N, Lee E, Weinberg Z, Moy R, Kim J, Link K, Breaker R. Riboswitches in Eubacteria Sense the Second Messenger Cyclic Di-GMP. Science 2008, 321: 411-413. PMID: 18635805, PMCID: PMC5304454, DOI: 10.1126/science.1159519.Peer-Reviewed Original ResearchConceptsCyclic di-GMPVirulence gene expressionGene expressionSecond messenger cyclic di-GMPNumerous fundamental cellular processesCyclic di-guanosine monophosphateFundamental cellular processesExpression of genesGMP riboswitchRiboswitch classesFlagellum biosynthesisBiofilm lifestyleCellular processesDiverse speciesPilus formationSecond messengerCell differentiationRiboswitchBacterial speciesMessenger RNARNA dinucleotideSpeciesExpressionPhysiological changesRegulonGene Regulation by Riboswitches
Breaker R. Gene Regulation by Riboswitches. The FASEB Journal 2008, 22: 97.3-97.3. DOI: 10.1096/fasebj.22.1_supplement.97.3.Peer-Reviewed Original ResearchGene expressionRiboswitch classesS-adenosylmethionineUntranslated regionWidespread riboswitch classesS-adenosylhomocysteineControl gene expressionDiversity of mechanismsGene regulationAlternative splicingModern organismsBacterial mRNAsUncharacterized mechanismRiboswitchRNA elementsMolecular switchFunctional potentialAptamer structureRNADiversityExpressionMRNAEukaryotesSplicingGenesRiboswitches as new antibiotics targets
Blount K, Breaker R. Riboswitches as new antibiotics targets. The FASEB Journal 2008, 22: 264.3-264.3. DOI: 10.1096/fasebj.22.1_supplement.264.3.Peer-Reviewed Original ResearchDrug targetsAntibacterial drug discoveryNew antibiotic targetsNew cellular targetsDrug discoveryAntibiotic targetsRiboswitchGene expressionRNA structureCellular targetsDrug discoverersAntibacterial compoundsGenesLethal effectsBacteriaExpressionMetabolite analogsReceptorsTargetDiscoveryRNABindsSelective receptorsMRNARecent work
2006
Riboswitches: Regulators of modern and ancient metabolism
Kim J, Breaker R. Riboswitches: Regulators of modern and ancient metabolism. The Biochemist 2006, 28: 11-15. DOI: 10.1042/bio02802011.Peer-Reviewed Original ResearchComplex biochemical pathwaysPrimitive life formsNucleic acid biochemistryAncient metabolismPrimitive organismsModern cellsLife formsStructured RNAsBiochemical pathwaysBiological processesEfficient enzymeRNARecent findingsMolecular sensorsSpecific receptorsSuch moleculesRiboswitchOrganismsRegulatorEnormous potentialEnzymePathwayBiochemistryMetabolismCellsGenetic control by riboswitches and ribozymes
Breaker R. Genetic control by riboswitches and ribozymes. The FASEB Journal 2006, 20: a455-a456. DOI: 10.1096/fasebj.20.4.a455-d.Peer-Reviewed Original ResearchGenetic switchGene expressionAptamer domainBacterial speciesCertain messenger RNAsControl gene expressionMessenger RNA stabilityNon-coding regionsComplex genetic elementsSelf-cleaving ribozymesRiboswitch classesReceptor-ligand interactionsTranscription elongationTranslation initiationRNA stabilityRNA transcriptionRiboswitchAllosteric changesGenetic controlGenetic elementsRNA structureMessenger RNATarget metabolitesRNARecent findingsRiboswitches as Genetic Control Elements
Nahvi A, Breaker R. Riboswitches as Genetic Control Elements. 2006, 89-106. DOI: 10.1007/978-0-387-47257-7_6.Peer-Reviewed Original ResearchGene control mechanismsCertain messenger RNAsGenetic control elementsGene expression systemRNA stabilityExpression platformRNA elementsExpression systemRiboswitchRNA structureLigand bindingMRNA transcriptionMessenger RNATarget metabolitesControl elementsTranscriptionControl mechanismsGenesRNABacteriaBindingExpressionTranslationMetabolitesAptamer