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 ResearchNatural 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
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 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 organismsGenetic 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
Evidence 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 sourceBacteriaComplexesRiboswitches
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 Research
2022
Ornate, large, extremophilic (OLE) RNA forms a kink turn necessary for OapC protein recognition and RNA function
Lyon S, Harris K, Odzer N, Wilkins S, Breaker R. Ornate, large, extremophilic (OLE) RNA forms a kink turn necessary for OapC protein recognition and RNA function. Journal Of Biological Chemistry 2022, 298: 102674. PMID: 36336078, PMCID: PMC9723947, DOI: 10.1016/j.jbc.2022.102674.Peer-Reviewed Original ResearchConceptsOLE RNARNP complexesRNA-protein binding assaysPrecise biochemical functionRNA structural motifsInability of cellsNatural binding sitesRibonucleoprotein complexesRNA functionBiochemical functionsExhibit phenotypesBacterial proteinsK-turnKink turnBacillus haloduransDisruptive mutationsSame proteinBacterial speciesProtein recognitionAnaerobic bacterial speciesFunctional roleSecondary structureRNAProteinOapB
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
The large, noncoding OLE RNA is associated with membrane biochemistry
Block K, Wallace J, Puerta‐Fernandez E, Breaker R. The large, noncoding OLE RNA is associated with membrane biochemistry. The FASEB Journal 2010, 24: 493.2-493.2. DOI: 10.1096/fasebj.24.1_supplement.493.2.Peer-Reviewed Original ResearchOLE RNAB. haloduransMembrane biochemistryMembrane-spanning proteinsHigh-throughput sequencingEnergy-generating pathwaysEscherichia coli cellsGel shift assaysNorthern blot analysisRNA fluorescenceSpecific ribonucleoproteinGram-positive bacteriaShift assaysColi cellsUnknown functionProbable binding siteSitu hybridizationBlot analysisBinding sitesHaloduransHoward Hughes Medical InstituteRNAProteinBiochemistryCells
2009
A plant 5S rRNA mimic regulates alternative splicing of transcription factor IIIA pre‐mRNAs
Hammond M, Wachter A, Breaker R. A plant 5S rRNA mimic regulates alternative splicing of transcription factor IIIA pre‐mRNAs. The FASEB Journal 2009, 23: 665.4-665.4. DOI: 10.1096/fasebj.23.1_supplement.665.4.Peer-Reviewed Original ResearchTranscription factor IIIAAlternative splicingDiverse plant lineagesRibosomal protein L5RNA polymerase IIIProtein-mRNA interactionsStructured RNA elementsPlant lineagesProtein L5Ribosomal componentsRibosomal RNAPolymerase IIIRNA elementsRRNA synthesisPrecursor mRNASplice productsStructural mimicrySplicingProtein expressionRRNARNAFunctional adaptationMRNANatural partnersLineages
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 protocolAmplificationGene 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
2007
Chapter 8
Link K, Breaker R. Chapter 8. 2007, 134-152. DOI: 10.1039/9781847557988-00134.Peer-Reviewed Original Research
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 findings