2025
Comprehensive mutational analysis of the sequence–function relationship within a viral internal ribosome entry site
Grunseich S, Strobel S. Comprehensive mutational analysis of the sequence–function relationship within a viral internal ribosome entry site. Nucleic Acids Research 2025, 53: gkaf445. PMID: 40421802, PMCID: PMC12107430, DOI: 10.1093/nar/gkaf445.Peer-Reviewed Original ResearchConceptsCrPV-IRESIRES functionViral internal ribosome entry siteNext-generation sequencing methodsInternal ribosome entry siteSequence-function relationshipsCricket paralysis virusRibosome entry siteCell-free systemComprehensive mutational analysisMechanism of translationHigh-throughput methodRibosome contactsIntergenic regionRNA elementsTranslation initiationSequence requirementsIRES elementsMutation databaseEukaryotic extractsInitiation factorsSequencing methodsExpressed proteinsHelical regionsMutation analysis
2024
Highly Reactive Group I Introns Ubiquitous in Pathogenic Fungi
Liu T, Pyle A. Highly Reactive Group I Introns Ubiquitous in Pathogenic Fungi. Journal Of Molecular Biology 2024, 436: 168513. PMID: 38447889, DOI: 10.1016/j.jmb.2024.168513.Peer-Reviewed Original ResearchGroup I intronsAntifungal drug targetsRNA metabolismPathogenic fungiPhylogeny of fungiSelf-splicing intronsDrug targetsSystemic fungal infectionsGenetic hotspotsRiboregulatory elementsMitochondrial intronsMitochondrial genesBioinformatics pipelineC. aurisCandida aurisRelevant fungiRNA elementsAspergillus fumigatusC. albicansHousekeeping genesCandida albicansNoncoding transcriptomeCryptococcus neoformansFungal infectionsFungiEngineered mRNA–ribosome fusions for facile biosynthesis of selenoproteins
Thaenert A, Sevostyanova A, Chung C, Vargas-Rodriguez O, Melnikov S, Söll D. Engineered mRNA–ribosome fusions for facile biosynthesis of selenoproteins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321700121. PMID: 38442159, PMCID: PMC10945757, DOI: 10.1073/pnas.2321700121.Peer-Reviewed Original ResearchConceptsSelenocysteine insertion sequenceRibosomal RNARibosome engineeringMessenger RNARegulatory RNA elementsMachinery of protein synthesisInsertion of SecSec-containing proteinsSite-specific insertionBiosynthesis of selenoproteinsNatural messenger RNALive bacterial cellsRNA elementsUAG codonInsertion sequenceRibosome structureUGA codonSec codonInsert SecStop codonSynthetic biologyDesigning proteinsRibosomePolypeptide chainBacterial cellsA compact regulatory RNA element in mouse Hsp70 mRNA
Wang W, Liu F, Ugalde M, Pyle A. A compact regulatory RNA element in mouse Hsp70 mRNA. NAR Molecular Medicine 2024, 1: ugae002. PMID: 38318492, PMCID: PMC10840451, DOI: 10.1093/narmme/ugae002.Peer-Reviewed Original ResearchOpen reading frameRNA elementsHeat shockOpen reading frame sequenceRegulatory RNA elementsSecondary structure modelMessenger RNACap-independent mannerCap-dependent translationMolecular chaperone functionSequences of HSP70Reading frameMisfolded proteinsRNA foldingRegulate protein expressionChaperone functionMRNA sequencesUntranslated regionShort stretchSecondary structureCell stressGene expressionHSP70 gene expressionStructural basisMolecular mechanisms
2023
Screening 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 target
2022
SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network
Li W, Yang S, Xu P, Zhang D, Tong Y, Chen L, Jia B, Li A, Lian C, Ru D, Zhang B, Liu M, Chen C, Fu W, Yuan S, Gu C, Wang L, Li W, Liang Y, Yang Z, Ren X, Wang S, Zhang X, Song Y, Xie Y, Lu H, Xu J, Wang H, Yu W. SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network. EBioMedicine 2022, 76: 103861. PMID: 35124429, PMCID: PMC8811534, DOI: 10.1016/j.ebiom.2022.103861.Peer-Reviewed Original ResearchConceptsHuman identical sequencesRNA elementsHuman genomeSARS-CoV-2 genomeHyaluronan synthase 2Chromatin immunoprecipitation assaysDistant genesSequence similarityGenomic fragmentsSequence identityTarget lociGenomic interactionsMiRNA precursorsH3K27ac enrichmentSARS-CoV-2Identical sequencesBioinformatics analysisImmunoprecipitation assaysGenomeGene expressionHEK293TQuantitative RT-PCRShort sequencesGenesHost enhancement
2021
Structural analyses of an RNA stability element interacting with poly(A)
Torabi SF, Chen YL, Zhang K, Wang J, DeGregorio SJ, Vaidya AT, Su Z, Pabit SA, Chiu W, Pollack L, Steitz JA. Structural analyses of an RNA stability element interacting with poly(A). Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2026656118. PMID: 33785601, PMCID: PMC8040590, DOI: 10.1073/pnas.2026656118.Peer-Reviewed Original ResearchConceptsRNA stability elementCis-acting RNA elementsGlobal conformational changesRich internal loopCryo-electron microscopyRice transposable elementsDiverse genomesDouble-helical regionsSmall-angle X-ray scatteringEne motifTransposable elementsGlobal structural changesRNA interactionsRNA stabilityBioinformatics studiesRNA elementsStability elementShort helixConformational changesDecay pathwaysInternal loopBiochemical structureTriplex structureBindingMotif
2019
Human chromatin remodeler cofactor, RNA interactor, eraser and writer sperm RNAs responding to obesity
Swanson GM, Estill M, Diamond MP, Legro RS, Coutifaris C, Barnhart KT, Huang H, Hansen KR, Trussell JC, Coward RM, Zhang H, Goodrich R, Krawetz SA. Human chromatin remodeler cofactor, RNA interactor, eraser and writer sperm RNAs responding to obesity. Epigenetics 2019, 15: 32-46. PMID: 31354029, PMCID: PMC6961666, DOI: 10.1080/15592294.2019.1644880.Peer-Reviewed Original ResearchConceptsSperm RNASperm DNA methylationChromosome organizationCoregulatory networkGene OntologyDNA methylationResponse pathwaysCellular stressRNA elementsRNAInteractorsErasersCofactorOvarian stimulation (AMIGOS) trialMethylationObesity-related inflammationTranscriptsMeasures of obesityAdipogenesisPathwayMultiple gestationsStimulation trialsAnimal modelsBMIHuman studies
2018
Carbodiimide reagents for the chemical probing of RNA structure in cells
Wang PY, Sexton AN, Culligan WJ, Simon MD. Carbodiimide reagents for the chemical probing of RNA structure in cells. RNA 2018, 25: 135-146. PMID: 30389828, PMCID: PMC6298570, DOI: 10.1261/rna.067561.118.Peer-Reviewed Original ResearchConceptsConformation of RNAU nucleotidesIntact cellsChemical probesDimethyl sulfateNucleotides of RNASingle-stranded nucleotidesXist lncRNACellular contextNoncoding RNAsRNA elementsSHAPE reagentsAccessible nucleotidesRNA conformationRNA structureBiological contextChemical probingWatson-Crick faceCellular environmentFunctional roleCarbodiimide reagentRNA nucleotidesRNANucleotidesStructured regionsHigh 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
2015
An RNA motif advances transcription by preventing Rho-dependent termination
Sevostyanova A, Groisman EA. An RNA motif advances transcription by preventing Rho-dependent termination. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e6835-e6843. PMID: 26630006, PMCID: PMC4687561, DOI: 10.1073/pnas.1515383112.Peer-Reviewed Original ResearchConceptsRho-dependent transcription terminationTranscription terminationRNA elementsNucleic Acid Binding ProteinsRho-dependent terminationOpen reading frameRNA polymeraseReading frameBacterial RNALeader regionRNA motifsRNA conformationRho's accessInefficient translationBinding proteinInactive complexPharmacological inhibitionRhoTranscription
2010
Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix
Mitton-Fry RM, DeGregorio SJ, Wang J, Steitz TA, Steitz JA. Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix. Science 2010, 330: 1244-1247. PMID: 21109672, PMCID: PMC3074936, DOI: 10.1126/science.1195858.Peer-Reviewed Original ResearchConceptsSarcoma-associated herpesvirusBox H/ACA small nucleolar RNAsMajor-groove triple helixNuclear noncoding RNANuclear retention elementSmall nucleolar RNAsViral RNA elementsRich internal loopTriple helixKaposi's sarcoma-associated herpesvirusPAN RNADeadenylation assaysRNA decayRNA clampNucleolar RNAsNoncoding RNAsNuclear RNATail recognitionRNA elementsFunctional importanceAngstrom resolutionRich loopSecondary structureRNAEne core
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 partnersLineagesA Conserved WD40 Protein Binds the Cajal Body Localization Signal of scaRNP Particles
Tycowski KT, Shu MD, Kukoyi A, Steitz JA. A Conserved WD40 Protein Binds the Cajal Body Localization Signal of scaRNP Particles. Molecular Cell 2009, 34: 47-57. PMID: 19285445, PMCID: PMC2700737, DOI: 10.1016/j.molcel.2009.02.020.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsBase SequenceCell LineChromatography, AffinityCoiled BodiesDrosophila melanogasterDrosophila ProteinsHeLa CellsHumansMolecular Sequence DataNucleic Acid ConformationRecombinant Fusion ProteinsRegulatory Sequences, Ribonucleic AcidRibonucleoproteinsRNA-Binding ProteinsSequence AlignmentConceptsCAB boxCB localizationSmall Cajal bodyWD40 proteinsRNP functionCajal bodiesLocalization signalACA motifDomain RNATelomerase RNAHuman homologPosttranscriptional modificationsSmall nuclearWDR79ScaRNAsRNA elementsCentral playerUV crosslinkNuclear RNPCore proteinRNAProteinAdditional interactionsBindingLocalization
2008
Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production
Pawlicki JM, Steitz JA. Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production. Journal Of Cell Biology 2008, 182: 61-76. PMID: 18625843, PMCID: PMC2447899, DOI: 10.1083/jcb.200803111.Peer-Reviewed Original ResearchMeSH KeywordsChromatinExonsHeLa CellsHumansIntronsMicroRNAsmRNA Cleavage and Polyadenylation FactorsNuclear ProteinsPolyadenylationRegulatory Sequences, Nucleic AcidRibonucleoproteinsRNA Polymerase IIIRNA Processing, Post-TranscriptionalRNA TransportRNA, MessengerRNA, ViralSequence DeletionSerine-Arginine Splicing FactorsSubcellular FractionsTranscription, GeneticConceptsPri-miRNAsTranscription sitesEndogenous pri-miRNAsPrimary miRNA transcriptsPri-miRNA processingSplicing factor SC35Viral RNA elementsHigh nuclear levelsMiRNA biogenesisMiRNA transcriptionMiRNA transcriptsNuclear stepsPrecursor miRNAsNuclear fociFactor SC35MicroRNA productionRNA elementsGene expressionTranscription leadNuclear fractionNuclear levelsTranscriptionMiRNAsProcessing signalsBiogenesisGene 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 structureRNADiversityExpressionMRNAEukaryotesSplicingGenes
2007
U2 snRNP Binds Intronless Histone Pre-mRNAs to Facilitate U7-snRNP-Dependent 3′ End Formation
Friend K, Lovejoy AF, Steitz JA. U2 snRNP Binds Intronless Histone Pre-mRNAs to Facilitate U7-snRNP-Dependent 3′ End Formation. Molecular Cell 2007, 28: 240-252. PMID: 17964263, PMCID: PMC2149891, DOI: 10.1016/j.molcel.2007.09.026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell NucleusDEAD-box RNA HelicasesHeLa CellsHistonesHumansIntronsMiceModels, MolecularOocytesProtein ConformationRibonucleoprotein, U2 Small NuclearRibonucleoprotein, U7 Small NuclearRibonucleoproteins, Small NuclearRNA 3' End ProcessingRNA PrecursorsRNA-Binding ProteinsRNA, MessengerTime FactorsXenopus laevis
2006
Identification of a Rapid Mammalian Deadenylation-Dependent Decay Pathway and Its Inhibition by a Viral RNA Element
Conrad NK, Mili S, Marshall EL, Shu MD, Steitz JA. Identification of a Rapid Mammalian Deadenylation-Dependent Decay Pathway and Its Inhibition by a Viral RNA Element. Molecular Cell 2006, 24: 943-953. PMID: 17189195, DOI: 10.1016/j.molcel.2006.10.029.Peer-Reviewed Original ResearchConceptsQuality control pathwaysViral RNA elementsPAN RNAPolyadenylated transcriptsMammalian cellsNuclear RNASuch transcriptsRNA elementsCellular RNAGene expressionNuclear accumulationNuclear extractsNaked RNARNADecay pathwaysTranscriptsDeadenylationDependent fashionPathwayDeadenylaseIntronsAccumulationMRNAHybridizationIntramolecular hybridizationRiboswitches 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
1998
A minor groove RNA triple helix within the catalytic core of a group I intron
Szewczak A, Ortoleva-Donnelly L, Ryder S, Moncoeur E, Strobel S. A minor groove RNA triple helix within the catalytic core of a group I intron. Nature Structural & Molecular Biology 1998, 5: 1037-1042. PMID: 9846872, DOI: 10.1038/4146.Peer-Reviewed Original Research
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