2022
Modulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells
Vijayakumar A, Park A, Steitz JA. Modulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells. Frontiers In Immunology 2022, 13: 828665. PMID: 35222412, PMCID: PMC8866245, DOI: 10.3389/fimmu.2022.828665.Peer-Reviewed Original Research
2021
Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts
Rosa-Mercado NA, Steitz JA. Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts. Trends In Biochemical Sciences 2021, 47: 206-217. PMID: 34489151, PMCID: PMC8840951, DOI: 10.1016/j.tibs.2021.08.003.Peer-Reviewed Original ResearchConceptsCellular stress responseHuman protein-coding genesStress responseProtein-coding genesDoG inductionNascent mRNAReadthrough transcriptionTranscriptional landscapeDifferent stress conditionsReadthrough transcriptsStress conditionsViral proteinsBiogenesisStress removalGenesTranscriptsCell exposureProduction playTranscriptionRNAProteinMRNAHostProductionHallmarkHyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression
Rosa-Mercado NA, Zimmer JT, Apostolidi M, Rinehart J, Simon MD, Steitz JA. Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression. Molecular Cell 2021, 81: 502-513.e4. PMID: 33400923, PMCID: PMC7867636, DOI: 10.1016/j.molcel.2020.12.002.Peer-Reviewed Original ResearchMeSH KeywordsDown-RegulationEndoribonucleasesHEK293 CellsHumansOsmotic PressureRNARNA Polymerase IISalt StressTime FactorsTranscription, GeneticTranscriptional ActivationConceptsWidespread transcriptional repressionTranscriptional repressionPol IIIntegrator complex subunitsRNA polymerase IIGenome-wide lossStress-induced redistributionParental genesTranscriptional outputDoG inductionPolymerase IIChIP sequencingHuman cell linesUpstream geneComplex subunitsPolyadenylation factorsTranscription profilesReadthrough transcriptsCatalytic subunitIntegrator activityCellular stressHyperosmotic stressTranscriptional levelTranscription resultsGenes
2017
Comparative analysis reveals genomic features of stress-induced transcriptional readthrough
Vilborg A, Sabath N, Wiesel Y, Nathans J, Levy-Adam F, Yario TA, Steitz JA, Shalgi R. Comparative analysis reveals genomic features of stress-induced transcriptional readthrough. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e8362-e8371. PMID: 28928151, PMCID: PMC5635911, DOI: 10.1073/pnas.1711120114.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGene Expression ProfilingGene Expression RegulationGenomeGenomicsHeat-Shock ResponseMiceNIH 3T3 CellsOsmotic PressureOxidative StressTranscription, GeneticConceptsTranscriptional readthroughReadthrough transcriptionGenomic featuresOsmotic stressProtein-coding gene lociHeat shockUnique chromatin signatureGenome-wide mappingOpen chromatin statePolymerase II occupancyNuclear RNA-seqGenome-wide studiesChromatin signaturesChromatin stateNIH 3T3 mouse fibroblast cellsNeighboring genesRNA classesReadthrough transcriptsReadthrough phenomenonRegulated processRNA-seqGene transcriptionGene locusStress responsePotential regulator
2016
Readthrough transcription: How are DoGs made and what do they do?
Vilborg A, Steitz JA. Readthrough transcription: How are DoGs made and what do they do? RNA Biology 2016, 14: 632-636. PMID: 26861889, PMCID: PMC5449079, DOI: 10.1080/15476286.2016.1149680.Peer-Reviewed Original ResearchConceptsDoG inductionDownstream of genesMammalian gene expressionLevel of transcriptionPervasive transcriptionIntergenic transcriptionTranscription terminationPossible molecular mechanismsTranscriptional readthroughOsmotic stressGene expressionMolecular mechanismsEndoplasmic reticulumTranscriptionIP3 receptorOutstanding questionsTranscriptsBiogenesisGenomeInductionReadthroughGenesCalcium releaseReticulumMechanism
2015
Widespread Inducible Transcription Downstream of Human Genes
Vilborg A, Passarelli MC, Yario TA, Tycowski KT, Steitz JA. Widespread Inducible Transcription Downstream of Human Genes. Molecular Cell 2015, 59: 449-461. PMID: 26190259, PMCID: PMC4530028, DOI: 10.1016/j.molcel.2015.06.016.Peer-Reviewed Original ResearchConceptsOsmotic stressLong non-coding regionsDownstream of genesProtein-coding genesNon-coding regionsPervasive transcriptionHuman cell linesTranscription downstreamHuman genomeHuman genesTranscript inductionRNA-seqPolyA signalUpstream transcriptsUndescribed mechanismGenesCell linesTranscriptionTranscript typeActive regulationTranscriptsDetailed mechanistic studiesRNADownstreamMechanistic studiesThe host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends
Xie M, Zhang W, Shu MD, Xu A, Lenis DA, DiMaio D, Steitz JA. The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends. Genes & Development 2015, 29: 1552-1564. PMID: 26220997, PMCID: PMC4526738, DOI: 10.1101/gad.266973.115.Peer-Reviewed Original ResearchConceptsEnd processing signalsSmall nuclear RNAProximity ligation assayEnd processingPre-miRNAsHerpesvirus saimiriPre-miRNA hairpinsRNA-protein interactionsSitu proximity ligation assayIntegrator complexMiRNA 3MiRNA biogenesisSnRNA 3Primary miRNAMiRNA hairpinsIntegrator activityNuclear RNASequence downstreamOncogenic γ-herpesvirusesRescue experimentsLigation assayVivo knockdownComplex actsΓ-herpesvirusesHairpin
2014
Versatile microRNA biogenesis in animals and their viruses
Xie M, Steitz JA. Versatile microRNA biogenesis in animals and their viruses. RNA Biology 2014, 11: 673-681. PMID: 24823351, PMCID: PMC4156499, DOI: 10.4161/rna.28985.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsMicroRNAsRibonuclease IIIRNA CapsRNA PrecursorsRNA Processing, Post-TranscriptionalTranscription, GeneticVirusesConceptsEssential cellular processesMiRNA regulatory networkPost-transcriptional levelUbiquitous gene regulatorsNon-canonical pathwayMost miRNAsCytoplasmic DicerMicroRNA biogenesisMolecular machineryCellular processesRegulatory networksPrimary transcriptGene regulatorsNuclear DroshaCellular RNABiogenesisDroshaAlternative mechanismFundamental roleCleavage stepMetazoansDicerMiRNAsMicroRNAsMiRNA
2012
EBV and human microRNAs co‐target oncogenic and apoptotic viral and human genes during latency
Riley KJ, Rabinowitz GS, Yario TA, Luna JM, Darnell RB, Steitz JA. EBV and human microRNAs co‐target oncogenic and apoptotic viral and human genes during latency. The EMBO Journal 2012, 31: 2207-2221. PMID: 22473208, PMCID: PMC3343464, DOI: 10.1038/emboj.2012.63.Peer-Reviewed Original ResearchConceptsHuman microRNAsLatent membrane protein 1Viral miRNA functionHigh-throughput sequencingHuman miRNA targetsMiRNA-binding sitesMiRNA functionEBV BHRF1Human genesMiRNA targetsMRNA targetsCellular miRNAsMembrane protein 1MiRNA clusterHuman miRNAsGene expressionCell cycleReporter assaysDistinct binding sitesViral mRNAsMiRNAsLytic genesLytic switchProtein 1EBV latent membrane protein 1
2009
Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function
Pawlicki JM, Steitz JA. Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function. Trends In Cell Biology 2009, 20: 52-61. PMID: 20004579, PMCID: PMC2821161, DOI: 10.1016/j.tcb.2009.10.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleusGene Regulatory NetworksHumansMicroRNAsRNA PrecursorsRNA SplicingTranscription, GeneticConceptsMature messenger RNAGene expressionRNA polymerase II transcriptsProtein-coding genesPolymerase II transcriptsRNA polymerase IIMessenger RNAPre-messenger RNARNA processing reactionsCotranscriptional eventsPolymerase IIProcessing eventsProcessing reactionsExtensive molecular interactionsEarly stepsTranscriptsRNAExquisite couplingMolecular interactionsMicroRNAsExpressionNuclear networkCrucial roleFinal fateSplicingSubnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: Processing at transcription sites or accumulation in SC35 foci
Pawlicki JM, Steitz JA. Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: Processing at transcription sites or accumulation in SC35 foci. Cell Cycle 2009, 8: 345-356. PMID: 19177009, PMCID: PMC3004524, DOI: 10.4161/cc.8.3.7494.Peer-Reviewed Original ResearchConceptsPri-miRNA processingPri-miRNAsTranscription sitesPrimary miRNA transcriptsPri-miRNA transcriptsPre-miRNA hairpinsRNA polymerase IIASF/SF2Splicing factor SC35Target messenger RNAsNumber of proteinsMiRNA biogenesisMiRNA transcriptsNuclear organizationMRNA metabolismPolymerase IINuclear fociProlyl isomeraseFactor SC35Subnuclear compartmentalizationPri-microRNAsMammalian cellsSC35 domainsGene expressionSC35
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 signalsBiogenesis
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 hybridizationMultiple domains of EBER 1, an Epstein-Barr virus noncoding RNA, recruit human ribosomal protein L22
Fok V, Mitton-Fry RM, Grech A, Steitz JA. Multiple domains of EBER 1, an Epstein-Barr virus noncoding RNA, recruit human ribosomal protein L22. RNA 2006, 12: 872-882. PMID: 16556938, PMCID: PMC1440895, DOI: 10.1261/rna.2339606.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCarrier ProteinsCell LineCross-Linking ReagentsElectrophoretic Mobility Shift AssayHerpesvirus 4, HumanHumansIn Vitro TechniquesMaltose-Binding ProteinsNucleic Acid ConformationPlasmidsProtein BindingProtein Structure, TertiaryRecombinant Fusion ProteinsRibosomal ProteinsRNA, UntranslatedRNA, ViralRNA-Binding ProteinsSequence DeletionTranscription, GeneticTransfectionUltraviolet Rays
2005
A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts
Conrad NK, Steitz JA. A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of intronless transcripts. The EMBO Journal 2005, 24: 1831-1841. PMID: 15861127, PMCID: PMC1142595, DOI: 10.1038/sj.emboj.7600662.Peer-Reviewed Original Research
1999
Guided tours: from precursor snoRNA to functional snoRNP
Weinstein L, Steitz J. Guided tours: from precursor snoRNA to functional snoRNP. Current Opinion In Cell Biology 1999, 11: 378-384. PMID: 10395551, DOI: 10.1016/s0955-0674(99)80053-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell NucleolusHumansRibonucleoproteins, Small NuclearRNA PrecursorsRNA, Small NuclearTranscription, Genetic
1998
Classification of gas5 as a Multi-Small-Nucleolar-RNA (snoRNA) Host Gene and a Member of the 5′-Terminal Oligopyrimidine Gene Family Reveals Common Features of snoRNA Host Genes
Smith C, Steitz J. Classification of gas5 as a Multi-Small-Nucleolar-RNA (snoRNA) Host Gene and a Member of the 5′-Terminal Oligopyrimidine Gene Family Reveals Common Features of snoRNA Host Genes. Molecular And Cellular Biology 1998, 18: 6897-6909. PMID: 9819378, PMCID: PMC109273, DOI: 10.1128/mcb.18.12.6897.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAnimalsBase SequenceCell DivisionCell NucleolusCloning, MolecularHumansMembrane ProteinsMiceMolecular Sequence DataMultigene FamilyProtein BiosynthesisRibonucleoproteinsRibosomesRNA SplicingRNA, AntisenseRNA, MessengerRNA, Small NuclearRNA, Small NucleolarTranscription, GeneticConceptsHost genesGene familyGAS5 geneBox C/D snoRNAsSnoRNA host genesHost gene transcriptsCell growthInhibition of translationSmall nucleolar RNA host geneSmall nucleolarD snoRNAsGAS5 transcriptsMRNP particlesSpecific transcriptsGene transcriptsGenesTranscriptsSnoRNAsRNASequenceIntronsCommon featureRibosomesRRNAFamily
1997
AU-rich elements target small nuclear RNAs as well as mRNAs for rapid degradation
Fan X, Myer V, Steitz J. AU-rich elements target small nuclear RNAs as well as mRNAs for rapid degradation. Genes & Development 1997, 11: 2557-2568. PMID: 9334320, PMCID: PMC316563, DOI: 10.1101/gad.11.19.2557.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, SurfaceBase SequenceELAV ProteinsELAV-Like Protein 1Gene Expression RegulationGenes, ReporterGlobinsHerpesvirus 2, SaimiriineMolecular Sequence DataMutationRepetitive Sequences, Nucleic AcidRibonucleasesRNA, MessengerRNA, Small NuclearRNA, ViralRNA-Binding ProteinsTranscription, GeneticTransfectionConceptsAU-rich elementsMRNA degradation machinerySmall nuclear RNAHSUR 1Host RNA moleculesDegradation machineryMammalian mRNAsNuclear RNARNA moleculesMutational analysisSequence requirementsTarget RNAHuR proteinOngoing translationRNA 1MRNARapid degradationRNASimilar mechanismDegradation activityDeadenylationSnRNAMachineryProteinDegradationA new strategy for introducing photoactivatable 4-thiouridine ((4S)U) into specific positions in a long RNA molecule.
Yu YT, Steitz JA. A new strategy for introducing photoactivatable 4-thiouridine ((4S)U) into specific positions in a long RNA molecule. RNA 1997, 3: 807-10. PMID: 9214662, PMCID: PMC1369526.Peer-Reviewed Original ResearchMeSH KeywordsAffinity LabelsBiochemistryDNA-Directed RNA PolymerasesPolymerase Chain ReactionRibonuclease HRNAThiouridineTranscription, GeneticConceptsPre-mRNAPre-mRNA substrateAT-AC intronsPhage RNA polymeraseRNA-DNA chimerasFull-length RNALong RNA moleculesRNA polymeraseRNA moleculesT4 RNA ligaseT4 DNA ligaseRNA ligaseDNA ligaseRNARNase H cleavageLigaseSpecific sitesSpecific positionsIntronsPolymeraseChimerasNew strategyCleavageOligonucleotideH cleavage
1995
Decreasing the distance between the two conserved sequence elements of histone pre-messenger RNA interferes with 3' processing in vitro.
Cho DC, Scharl EC, Steitz JA. Decreasing the distance between the two conserved sequence elements of histone pre-messenger RNA interferes with 3' processing in vitro. RNA 1995, 1: 905-14. PMID: 8548655, PMCID: PMC1369339.Peer-Reviewed Original ResearchAnimalsBase SequenceBinding SitesConserved SequenceHistonesMolecular Sequence DataMRNA Cleavage and Polyadenylation FactorsNuclear ProteinsNucleic Acid ConformationRibonucleoproteins, Small NuclearRNA PrecursorsRNA Processing, Post-TranscriptionalRNA-Binding ProteinsRNA, MessengerSequence DeletionSubstrate SpecificityTranscription, Genetic