2021
STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts
Zimmer JT, Rosa-Mercado NA, Canzio D, Steitz JA, Simon MD. STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts. Molecular Cell 2021, 81: 4398-4412.e7. PMID: 34520723, PMCID: PMC9020433, DOI: 10.1016/j.molcel.2021.08.019.Peer-Reviewed Original ResearchConceptsPause releaseRNA polymerase II transcriptsRNA polymerase II moleculesCis-acting DNA elementsTATA box-containing promotersPolymerase II transcriptsPromoter-proximal pausingCritical regulatory functionsTranscriptional regulationRNA turnoverTranscriptional controlDNA elementsTranscriptional shutdownPause sitesHyperosmotic stressRegulatory mechanismsRegulatory functionsPrinciples of regulationHormonal stimuliPausingPremature terminationTranscriptsRegulation
2018
Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal
Sabath N, Vilborg A, Steitz JA, Shalgi R. Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal. Human Genomics 2018, 12: 32. PMID: 29945683, PMCID: PMC6020437, DOI: 10.1186/s40246-018-0164-4.Peer-Reviewed Original ResearchConceptsTranscription start siteTranscriptional readthroughStart siteOsmotic stressProtein-coding genesGenome-wide comparisonEnd of genesStress-mediated inductionMammalian stress responseNIH3T3 mouse cellsDe novo initiationTranscription initiationGene endMammalian cellsLong transcriptsNIH3T3 cellsMouse cellsSimilar transcriptsStress responseTSS-seqHuman cellsReadthroughNovo initiationDramatic inductionStress conditions
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
2015
A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting
Herbert KM, Sarkar SK, Mills M, De la Herran H, Neuman KC, Steitz JA. A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting. RNA 2015, 22: 175-183. PMID: 26683315, PMCID: PMC4712668, DOI: 10.1261/rna.054684.115.Peer-Reviewed Original ResearchConceptsPri-miRNA substratesMicroprocessor complexHeterotrimeric complexDeletion constructsSingle-molecule subunit countingRNA-binding proteinFull-length proteinAbsence of RNAStem-loop structureSingle-molecule photobleachingSize exclusion chromatographyPresence of RNARNaseIII enzymesPhotobleaching assaysMicroRNA biogenesisSubunit countingMammalian cellsDroshaDGCR8Fluorescent proteinHuman cellsMultiple copiesRNAProteinExact stoichiometryWidespread 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 studiesViral noncoding RNAs: more surprises
Tycowski KT, Guo YE, Lee N, Moss WN, Vallery TK, Xie M, Steitz JA. Viral noncoding RNAs: more surprises. Genes & Development 2015, 29: 567-584. PMID: 25792595, PMCID: PMC4378190, DOI: 10.1101/gad.259077.115.Peer-Reviewed Original ResearchConceptsDiverse biological rolesSmall noncoding RNAsMultitude of functionsHost immune evasionEukaryotic cellsCellular transformationNoncoding RNAsHost counterpartsAnimal virusesBiological roleNcRNAsRNA virusesViral ncRNAsMechanism of actionImmune evasionViral replicationMore surprisesBiogenesisViral persistenceRNAProteinDNAVirusRegulationReplication
2014
Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function
Guo YE, Riley KJ, Iwasaki A, Steitz JA. Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function. Molecular Cell 2014, 54: 67-79. PMID: 24725595, PMCID: PMC4039351, DOI: 10.1016/j.molcel.2014.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteBase SequenceCallithrixEnzyme ActivationGene Expression RegulationGPI-Linked ProteinsGRB2 Adaptor ProteinHEK293 CellsHerpesvirus 2, SaimiriineHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansImmunoprecipitationInterferon-gammaJurkat CellsLectins, C-TypeLymphocyte ActivationMicroRNAsMitogen-Activated Protein KinasesMolecular Sequence DataReceptors, Antigen, T-CellRNA StabilityRNA, UntranslatedRNA, ViralSemaphorinsSequence Analysis, RNASignal TransductionT-LymphocytesTime FactorsTransfectionConceptsMitogen-activated protein kinaseMiR-27Protein coding genesHerpesvirus saimiriHigh-throughput sequencingTCR-induced activationCell functionHSUR 1Γ-herpesvirusesNoncoding RNAsProtein kinaseEctopic expressionOncogenic γ-herpesvirusesTarget genesInduction of CD69MicroRNA-27Key modulatorRNACommon targetAlHV-1GenesCell receptorDiverse strategiesHost T-cell functionCellsThe Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones
Cech TR, Steitz JA. The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones. Cell 2014, 157: 77-94. PMID: 24679528, DOI: 10.1016/j.cell.2014.03.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChromatinGene Expression RegulationGenomeHumansRibonucleoproteinsRNA, CatalyticRNA, Long NoncodingRNA, UntranslatedConceptsBiological functionsRNA-protein complexesLevel of transcriptionForeign nucleic acidsMost ncRNAsLong ncRNAsNcRNA researchRNA processingGenome rearrangementsNucleic acidsNoncoding RNAsGene expressionRNA structureNcRNAsBase pairingDNA synthesisRemarkable varietySnoRNPsRiboswitchGenomeSnRNPsRNAsRibosomesTranscriptionTelomerase
2011
Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA–protein complexes (microRNPs)
Mortensen RD, Serra M, Steitz JA, Vasudevan S. Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA–protein complexes (microRNPs). Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8281-8286. PMID: 21536868, PMCID: PMC3100953, DOI: 10.1073/pnas.1105401108.Peer-Reviewed Original ResearchConceptsMicroRNA–protein complexesProtein kinase AIIXenopus laevis oocytesImmature Xenopus laevis oocytesGene expression activationMammalian cell linesLaevis oocytesHuman Ago2Target reporterMammalian cellsExpression activationMyt1 kinaseGene expressionPosttranscriptional activationRegulated expressionSpecific mRNAsPhysiological relevanceQuiescent cellsMicroRNAsOocyte stateCell linesOocytesReporterCAMP levelsExpression
2009
miRNPs: versatile regulators of gene expression in vertebrate cells1
Steitz JA, Vasudevan S. miRNPs: versatile regulators of gene expression in vertebrate cells1. Biochemical Society Transactions 2009, 37: 931-935. PMID: 19754429, DOI: 10.1042/bst0370931.Peer-Reviewed Original ResearchConceptsPost-transcriptional controlAssociation of Ago2Role of miRNAsImmature Xenopus oocytesTNFalpha AREProtein FXR1Contact-inhibited cellsTranslational regulationTranslation activationVersatile regulatorsTranslational efficiencyNegative regulatorGene expressionSpecific miRNACell cycleEffector moleculesCell growthXenopus oocytesAgo2FXR1
2008
Cell cycle control of microRNA-mediated translation regulation
Vasudevan S, Tong Y, Steitz JA. Cell cycle control of microRNA-mediated translation regulation. Cell Cycle 2008, 7: 1545-1549. PMID: 18469529, PMCID: PMC2556257, DOI: 10.4161/cc.7.11.6018.Peer-Reviewed Original Research
2007
Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation
Vasudevan S, Tong Y, Steitz JA. Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation. Science 2007, 318: 1931-1934. PMID: 18048652, DOI: 10.1126/science.1149460.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsArgonaute ProteinsBase PairingCell CycleCell LineCell ProliferationComputational BiologyEukaryotic Initiation Factor-2Gene Expression RegulationHeLa CellsHMGA2 ProteinHumansInterphaseMicroRNAsProtein BiosynthesisRibonucleoproteinsRNA-Binding ProteinsRNA, MessengerTransfectionTumor Necrosis Factor-alphaUp-RegulationConceptsAU-rich elementsCell cycle arrestCycle arrestUntranslated regionMental retardation-related protein 1MicroRNA target sitesMicroRNA let-7Messenger RNA (mRNA) 3' untranslated regionsRegulates TranslationTranslation regulationTarget mRNAsGene expressionCell cycleCommon functionProtein 1ArgonauteTarget siteActivation signalsRepressionTumor necrosis factor-alpha mRNAMRNARegulationActivationArrestMicroRNPsTarget mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR
Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 9667-9672. PMID: 17535905, PMCID: PMC1887587, DOI: 10.1073/pnas.0703820104.Peer-Reviewed Original ResearchConceptsInternal ribosome entry siteTarget mRNAsMiRNA-mediated repressionRepression of translationLuciferase reporter mRNAMiRNA target sitesInitiation of translationMiRNA-binding sitesHuman HeLa cellsRibosome entry siteMicroRNA-binding sitesLet-7 complementary sitesHuman Ago2Reporter mRNAMicroRNAs (miRNAs) bindEndogenous mRNATranslational efficiencyLet-7a miRNAUTRProtein synthesisDNA transfectionComplementary sitesHeLa cellsEntry siteTarget site
2004
Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay
Hirose T, Shu MD, Steitz JA. Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17976-17981. PMID: 15608055, PMCID: PMC539812, DOI: 10.1073/pnas.0408435102.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCell NucleusCodon, NonsenseDNA, ComplementaryEvolution, MolecularExonsGene Expression RegulationHeLa CellsHumansImmunoprecipitationIntronsMutagenesis, Site-DirectedOpen Reading FramesPlasmidsRibonuclease HRibonucleoproteins, Small NuclearRNARNA PrecursorsRNA SplicingRNA, MessengerRNA, Small NuclearSpliceosomesTime FactorsTransfectionConceptsExon junction complexU12-type intronsOpen reading frameNonsense-mediated mRNA decayU12-type spliceosomeNonsense-mediated decaySmall nuclear ribonucleoproteinU2-type spliceosomePremature termination codonEJC assemblyMetazoan cellsMRNA decayEvolutionary ageDownstream functionsIntron removalNuclear ribonucleoproteinReading frameExon junctionsTermination codonJunction complexGene expressionIntron downstreamSpliceosomeIntronsSplicing
2003
Splicing-Dependent and -Independent Modes of Assembly for Intron-Encoded Box C/D snoRNPs in Mammalian Cells
Hirose T, Shu MD, Steitz JA. Splicing-Dependent and -Independent Modes of Assembly for Intron-Encoded Box C/D snoRNPs in Mammalian Cells. Molecular Cell 2003, 12: 113-123. PMID: 12887897, DOI: 10.1016/s1097-2765(03)00267-3.Peer-Reviewed Original ResearchConceptsBox C/D snoRNAsSplice siteSnoRNP proteinsD snoRNAsSnoRNP assemblyMammalian cellsHost intronBox C/D snoRNPsSmall nucleolar RNAsD snoRNPsRRNA modificationNucleolar RNAsHost genesActive splicingNts upstreamIntronsEfficient expressionSnoRNAsStable stemSplicingVivo analysisProteinAssemblyBlockage experimentsStem
2002
The splicing of U12‐type introns can be a rate‐limiting step in gene expression
Patel AA, McCarthy M, Steitz JA. The splicing of U12‐type introns can be a rate‐limiting step in gene expression. The EMBO Journal 2002, 21: 3804-3815. PMID: 12110592, PMCID: PMC126102, DOI: 10.1093/emboj/cdf297.Peer-Reviewed Original ResearchConceptsU12-type intronsGene expressionDrosophila melanogaster S2 cellsProtein-coding genesU12-type spliceosomePost-transcriptional regulationHuman tissue culture cellsU2-type intronsMetazoan genomesTissue culture cellsS2 cellsU12-typeIntron removalIdentical mRNAIntronsFluorescent proteinQuantitative RT-PCR assayMinigene constructsCulture cellsRate-limiting stepSpliceosomeMRNAMinor classExpressionRT-PCR assays
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-Binding ProteinsRNA, MessengerRNA, Small NuclearRNA, ViralTranscription, GeneticTransfectionConceptsAU-rich elementsMRNA degradation machinerySmall nuclear RNAHSUR 1Host RNA moleculesDegradation machineryMammalian mRNAsNuclear RNARNA moleculesMutational analysisSequence requirementsTarget RNAHuR proteinOngoing translationRNA 1MRNARapid degradationRNASimilar mechanismDegradation activityDeadenylationSnRNAMachineryProteinDegradationIdentification of HuR as a protein implicated in AUUUA‐mediated mRNA decay
Myer V, Fan X, Steitz J. Identification of HuR as a protein implicated in AUUUA‐mediated mRNA decay. The EMBO Journal 1997, 16: 2130-2139. PMID: 9155038, PMCID: PMC1169815, DOI: 10.1093/emboj/16.8.2130.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsAntigens, SurfaceBase CompositionCell ExtractsCross-Linking ReagentsELAV ProteinsELAV-Like Protein 1Gene Expression RegulationHeLa CellsHumansMiceMolecular Sequence DataMolecular WeightRegulatory Sequences, Nucleic AcidRNA-Binding ProteinsRNA, MessengerUltraviolet RaysConceptsAU-rich elementsMRNA decayUntranslated regionRNA-binding specificityARE-binding proteinsHeLa nuclear extractsGene familyMRNA degradationNuclear extractsEssential signalMessenger RNAProteinSequence's abilityHuRAUUUARapid degradationCritical roleHuR.RNAMachineryMRNADegradationRegulationSubsequent analysisExpression
1982
Nucleotide sequence of γδ resolvase gene and demonstration that its gene product acts as a repressor of transcription
Reed R, Shibuya G, Steitz J. Nucleotide sequence of γδ resolvase gene and demonstration that its gene product acts as a repressor of transcription. Nature 1982, 300: 381-383. PMID: 6292730, DOI: 10.1038/300381a0.Peer-Reviewed Original ResearchConceptsRepressor of transcriptionSite-specific recombination systemResolvase proteinAmino acid sequenceSite-specific recombinationElement-encoded proteinsIntercistronic regionGene initiatesFrequency of transpositionGene productsNucleotide sequenceAcid sequenceRecombination systemTranscription systemGenetic analysisΓδ resolvaseResolvaseGenesTranscriptionProteinResolvase geneRelated transposonsTransposaseModel substrateRecombination