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 ResearchNa+ riboswitches regulate genes for diverse physiological processes in bacteria
White N, Sadeeshkumar H, Sun A, Sudarsan N, Breaker RR. Na+ riboswitches regulate genes for diverse physiological processes in bacteria. Nature Chemical Biology 2022, 18: 878-885. PMID: 35879547, PMCID: PMC9337991, DOI: 10.1038/s41589-022-01086-4.Peer-Reviewed Original ResearchConceptsOsmotic stressGene expressionDiverse physiological processesMetal ion transportersGene expression changesExpression of genesRiboswitch classesBacterial proteinsIon transportersExpression changesPhysiological processesATP productionLow mM rangeGenesProteinExpressionBacteriaTranscriptionDissociation constantsOrganismsBiologyMM rangeTransportersMotifStressNatural circularly permuted group II introns in bacteria produce RNA circles
Roth A, Weinberg Z, Vanderschuren K, Murdock MH, Breaker RR. Natural circularly permuted group II introns in bacteria produce RNA circles. IScience 2021, 24: 103431. PMID: 34901790, PMCID: PMC8637638, DOI: 10.1016/j.isci.2021.103431.Peer-Reviewed Original ResearchStructure of a bacterial OapB protein with its OLE RNA target gives insights into the architecture of the OLE ribonucleoprotein complex
Yang Y, Harris KA, Widner DL, Breaker RR. Structure of a bacterial OapB protein with its OLE RNA target gives insights into the architecture of the OLE ribonucleoprotein complex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2020393118. PMID: 33619097, PMCID: PMC7936274, DOI: 10.1073/pnas.2020393118.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBacillusBacterial ProteinsBase SequenceBinding SitesCloning, MolecularCrystallography, X-RayEscherichia coliGene ExpressionGene Expression Regulation, BacterialGenetic VectorsMolecular Docking SimulationNucleic Acid ConformationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant ProteinsRibonucleoproteinsRNA, BacterialRNA, UntranslatedConceptsOLE RNARNP complexesBiological functionsBacterial noncoding RNAsRNA-binding surfaceProtein-RNA interfacesHigh-resolution structuresUnique structural elementsKOW motifProtein partnersHigh conservationRibonucleoprotein complexesRNA classesRNA interactionsNoncoding RNAsBacterial responseOapBRNA targetsRNA fragmentsAtomic detailRNAProtein BMolecular contactsProtein AStructural features
2024
Improved methods for genetic manipulation of the alkaliphile Halalkalibacterium halodurans
Wencker F, Lyon S, Breaker R. Improved methods for genetic manipulation of the alkaliphile Halalkalibacterium halodurans. Frontiers In Microbiology 2024, 15: 1465811. PMID: 39360312, PMCID: PMC11445130, DOI: 10.3389/fmicb.2024.1465811.Peer-Reviewed Original ResearchProspects 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 elementsPoolBioinformatic prediction of proteins relevant to functions of the bacterial OLE ribonucleoprotein complex
Fernando C, Breaker R. Bioinformatic prediction of proteins relevant to functions of the bacterial OLE ribonucleoprotein complex. MSphere 2024, 9: e00159-24. PMID: 38771028, PMCID: PMC11332333, DOI: 10.1128/msphere.00159-24.Peer-Reviewed Original ResearchOLE RNANoncoding RNA classesRNP complexesRNA classesSequence conservationProtein partnersBiochemical functionsDiverse stress conditionsProtein binding partnersEmergence of proteinsPhylogenetic profilesRibonucleoprotein complexSpore formationBacterial speciesCellular stressExtremophilic bacteriaProtein componentsRibonucleoproteinGenetic disruptionRNATransport proteinsRelevant to functionBioinformatics predictionGram-positivePrimitive organismsThe discovery of novel noncoding RNAs in 50 bacterial genomes
Narunsky A, Higgs G, Torres B, Yu D, de Andrade G, Kavita K, Breaker R. The discovery of novel noncoding RNAs in 50 bacterial genomes. Nucleic Acids Research 2024, 52: 5152-5165. PMID: 38647067, PMCID: PMC11109978, DOI: 10.1093/nar/gkae248.Peer-Reviewed Original ResearchBacterial genomesDomains of lifeIntergenic regionNcRNA classesGC-rich intergenic regionsBacterial domain of lifeIndividual bacterial genomesStructured noncoding RNAsNovel noncoding RNAsProtein coding genesNoncoding RNAsNcRNA motifsRiboswitch candidatesBacterial domainRiboswitch classesCoding genesGene regulationCellular processesCytidine nucleotidesBacterial speciesGenomeComputational pipelineNcRNAsDiverse functionsGenesGenetic disruption of the bacterial raiA motif noncoding RNA causes defects in sporulation and aggregation
Soares L, King C, Fernando C, Roth A, Breaker R. Genetic disruption of the bacterial raiA motif noncoding RNA causes defects in sporulation and aggregation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2318008121. PMID: 38306478, PMCID: PMC10861870, DOI: 10.1073/pnas.2318008121.Peer-Reviewed Original ResearchConceptsMotif RNAsGenetic disruptionSecondary structure modelKnock-out strainTrans-acting factorsNoncoding RNAsCell differentiation processAbundant RNATransfer RNANcRNA classesRibosomal RNASpore formationMotif genesCellular processesBacterial speciesCellular functionsBioinformatics analysisExpression analysisMotifRNAGenesBiochemical mechanismsNcRNAsDifferentiation processStructural probesDisruption of the bacterial OLE RNP complex impairs growth on alternative carbon sources
Lyon S, Wencker F, Fernando C, Harris K, Breaker R. Disruption of the bacterial OLE RNP complex impairs growth on alternative carbon sources. PNAS Nexus 2024, 3: pgae075. PMID: 38415217, PMCID: PMC10898510, DOI: 10.1093/pnasnexus/pgae075.Peer-Reviewed Original ResearchRNP complexesMinimal mediumWild-type cellsAlternative carbon sourcesUnfavorable growth conditionsOLE RNASuppressor selectionDiverse stressesCarbon/energy sourceProtein secretionCarbon sourceGenetic disruptionCellular adaptationNoncoding RNAsFunctional linkRNAGrowth conditionsRibonucleoproteinImpaired growthPhosphate homeostasisFundamental processesHomeostasisShort-chain alcoholsElevated MgCarbon/energy
2023
A spermidine riboswitch class in bacteria exploits a close variant of an aptamer for the enzyme cofactor S-adenosylmethionine
Salvail H, Balaji A, Roth A, Breaker R. A spermidine riboswitch class in bacteria exploits a close variant of an aptamer for the enzyme cofactor S-adenosylmethionine. Cell Reports 2023, 42: 113571. PMID: 38096053, PMCID: PMC10853860, DOI: 10.1016/j.celrep.2023.113571.Peer-Reviewed Original Research8-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 derivativesExpressionVariantsEvidence that OLE RNA is a component of a major stress‐responsive ribonucleoprotein particle in extremophilic bacteria
Breaker R, Harris K, Lyon S, Wencker F, Fernando C. Evidence that OLE RNA is a component of a major stress‐responsive ribonucleoprotein particle in extremophilic bacteria. Molecular Microbiology 2023, 120: 324-340. PMID: 37469248, DOI: 10.1111/mmi.15129.Peer-Reviewed Original ResearchConceptsOLE RNAPrecise biochemical functionFundamental cellular processesCell growthTOR complexesProtein partnersRibonucleoprotein complexesCellular processesRNP complexesBiochemical functionsGram-positive bacteriaNoncoding RNAsRibonucleoprotein particleExtremophilic bacteriaBacterial speciesGenetic disruptionStress conditionsDiverse pathwaysRNAMetabolic adaptationCell membraneExtreme environmentsCarbon sourceBacteriaComplexesIn 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 typesSequenceA conserved uORF in the ilvBNC mRNA of Corynebacterium species regulates ilv operon expression
Narunsky A, Kavita K, Panchapakesan S, Fris M, Breaker R. A conserved uORF in the ilvBNC mRNA of Corynebacterium species regulates ilv operon expression. Microbial Genomics 2023, 9: mgen001019. PMID: 37233150, PMCID: PMC10272879, DOI: 10.1099/mgen.0.001019.Peer-Reviewed Original ResearchConceptsBranched-chain amino acidsRNA motifsUpstream open reading framesTranscription attenuation mechanismStructured noncoding RNAsOpen reading frameRiboswitch classesTranscription attenuationProtein translationNoncoding RNAsOperon expressionGenetic approachesReading frameStart codonUORF translationStop codonBacterial speciesHost cellsGenesUORFsAmino acidsMotifCodonCommon mechanismCorynebacterium speciesRiboswitches
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