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 ResearchConceptsWidespread 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
Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover
Rosa-Mercado NA, Withers JB, Steitz JA. Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover. Genes & Development 2017, 31: 957-958. PMID: 28637691, PMCID: PMC5495124, DOI: 10.1101/gad.302695.117.Peer-Reviewed Original ResearchConceptsPre-mRNA splicing eventsPost-transcriptional modificationsMRNA biogenesisDifferent subcellular fractionsMRNA biologySplicing eventsMature mRNABiochemical approachesRNA transcriptsPivotal regulatorMethylation levelsHeLa cellsSubcellular fractionsRNA nucleosidesMethylationTranscriptsBiogenesisChromatinSplicingMethyladenosineExonsGenesRNABiologyRegulator
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 releaseReticulumMechanismCalcium signaling and transcription: elongation, DoGs, and eRNAs.
Vilborg A, Passarelli MC, Steitz JA. Calcium signaling and transcription: elongation, DoGs, and eRNAs. Receptors & Clinical Investigation 2016, 3 PMID: 29147672, PMCID: PMC5685190, DOI: 10.14800/rci.1169.Peer-Reviewed Original ResearchGene-specific transcription factorsPhases of transcriptionCertain stress conditionsTranscription terminationReadthrough transcriptionTranscription initiationAlternative splicingCellular processesTranscription factorsRegulated processKey intracellularSignaling cascadesTranscriptionCalcium signalingStress conditionsDiverse classSuch CaERNAsSplicingGenesTranscriptsSignalingCalcium ionsIntracellularCascade
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 studies
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 TransductionTime FactorsT-LymphocytesTransfectionConceptsMitogen-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 functionCells
2005
GAS5 Gene
Hirose T, Steitz J. GAS5 Gene. 2005 DOI: 10.1038/npg.els.0005019.Peer-Reviewed Original Research
2002
Branchpoint selection in the splicing of U12-dependent introns in vitro.
McConnell TS, Cho SJ, Frilander MJ, Steitz JA. Branchpoint selection in the splicing of U12-dependent introns in vitro. RNA 2002, 8: 579-86. PMID: 12022225, PMCID: PMC1370279, DOI: 10.1017/s1355838202028029.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceHumansIn Vitro TechniquesIntronsModels, GeneticPol1 Transcription Initiation Complex ProteinsRibonucleoproteins, Small NuclearRibosomal ProteinsRNARNA SplicingRNA-Binding ProteinsSaccharomyces cerevisiae ProteinsSpliceosomesTranscription FactorsXenopusXenopus ProteinsConceptsU12-dependent intronsU12-type intronsSixth intronBranchpoint sequenceSplicing of intronsU12-type splicingU12-type spliceosomeU12-dependent splicingBase-pairing mechanismHeLa nuclear extractsAdditional intronConsecutive adenosinesSplicing substrateThird intronU12 snRNAHuman p120First intronIntronsNuclear extractsSplicingGenesBranch sitePathwayBranchpointP120
2001
Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs
Tycowski K, Steitz J. Non-coding snoRNA host genes in Drosophila: expression strategies for modification guide snoRNAs. European Journal Of Cell Biology 2001, 80: 119-125. PMID: 11302516, DOI: 10.1078/0171-9335-00150.Peer-Reviewed Original ResearchConceptsSnoRNA host genesModification-guide snoRNAsHost genesGuide snoRNAsSplice siteDifferent eukaryotic kingdomsEukaryotic kingdomsPolycistronic unitsD. melanogasterProtein codingTranslational apparatusConserved distanceSnoRNA sequencesTrailer sequencesIntron lariatPrimary transcriptFunctional proteinsNucleotides upstreamExpression strategyExonucleolytic activitySnoRNAsIntronsGenesDebranching activityProtein
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
1996
A small nucleolar RNA requirement for site-specific ribose methylation of rRNA in Xenopus
Tycowski K, Smith C, Shu M, Steitz J. A small nucleolar RNA requirement for site-specific ribose methylation of rRNA in Xenopus. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 14480-14485. PMID: 8962077, PMCID: PMC26158, DOI: 10.1073/pnas.93.25.14480.Peer-Reviewed Original ResearchConceptsSmall nucleolar RNA (snoRNA) speciesSite-specific ribose methylationXenopus oocyte systemSnoRNA speciesSnoRNA genesRibose methylationVertebrate cellsRNA speciesMultiple homologsSnoRNA stabilityRRNASnoRNAsOocyte systemRNA requirementsXenopusXenopus oocytesFibrillarinMethylationSpeciesOocytesVertebratesHomologCloningGenesTranscriptsA Novel Spliceosome Containing U11, U12, and U5 snRNPs Excises a Minor Class (AT–AC) Intron In Vitro
Tarn W, Steitz J. A Novel Spliceosome Containing U11, U12, and U5 snRNPs Excises a Minor Class (AT–AC) Intron In Vitro. Cell 1996, 84: 801-811. PMID: 8625417, DOI: 10.1016/s0092-8674(00)81057-0.Peer-Reviewed Original ResearchMeSH KeywordsBase CompositionBase SequenceBlotting, NorthernCell NucleusHeLa CellsHumansMolecular Sequence DataNucleic Acid ConformationOligodeoxyribonucleotidesPlasmidsPolymerase Chain ReactionRibonuclease HRibonucleoprotein, U5 Small NuclearRibonucleoproteins, Small NuclearRNA PrecursorsRNA SplicingConceptsU5 small nuclear ribonucleoproteinSmall nuclear ribonucleoproteinU12 small nuclear ribonucleoproteinsMinor class intronsProtein coding genesPre-mRNA substrateNative gel electrophoresisCoding genesBranch site sequenceSplicing complexesNuclear ribonucleoproteinPre-mRNAP120 geneLariat intermediateSite sequenceIntronsHeLa cellsEssential roleSplicingGel electrophoresisBranch siteGenesU12Minor classU11A mammalian gene with introns instead of exons generating stable RNA products
Tycowski K, Shu M, Steitz J. A mammalian gene with introns instead of exons generating stable RNA products. Nature 1996, 379: 464-466. PMID: 8559254, DOI: 10.1038/379464a0.Peer-Reviewed Original ResearchConceptsProtein-coding genesRibosomal subunit assemblyRibosomal RNA transcriptionSmall nucleolar RNAsMammalian genesSnoRNA genesEukaryotic cellsProtein codingMature rRNANucleolar RNAsHost genesSubunit assemblyDifferent intronsRNA transcriptionRNA productsExtensive complementarityIntronsGenesSnoRNAsExonsRNARRNATranscriptionPolysomesMaturation1
1995
U12 snRNA in vertebrates: evolutionary conservation of 5' sequences implicated in splicing of pre-mRNAs containing a minor class of introns.
Tarn WY, Yario TA, Steitz JA. U12 snRNA in vertebrates: evolutionary conservation of 5' sequences implicated in splicing of pre-mRNAs containing a minor class of introns. RNA 1995, 1: 644-56. PMID: 7489523, PMCID: PMC1369308.Peer-Reviewed Original ResearchConceptsU12 snRNASnRNA genesMinor class intronsRNA polymerase IIU6 snRNA sequencesMinor classPutative branch siteNoncanonical splice sitesMajor classesEvolutionary conservationBranch site sequencePolymerase IIU2 genesFunctional genesSnRNA sequencesIntronsConsensus sequenceSnRNASite sequenceUpstream elementSplice siteSplicingGenesTranscriptionBranch site
1994
Requirement for Intron-Encoded U22 Small Nucleolar RNA in 18S Ribosomal RNA Maturation
Tycowski K, Shu M, Steitz J. Requirement for Intron-Encoded U22 Small Nucleolar RNA in 18S Ribosomal RNA Maturation. Science 1994, 266: 1558-1561. PMID: 7985025, DOI: 10.1126/science.7985025.Peer-Reviewed Original ResearchConceptsRibosomal RNASmall RNAsProtein-coding gene transcriptsRibosomal RNA maturationSmall nucleolar RNAsRNA maturationVertebrate cellsCellular functionsNucleolar RNAsHost genesIntron fragmentGene transcriptsRNAXenopus oocytesU22IntronsGenesTranscriptsNucleoliOocytesMaturationTargetingCellsFragmentsDepletion
1991
Multiple processing-defective mutations in a mammalian histone pre-mRNA are suppressed by compensatory changes in U7 RNA both in vivo and in vitro.
Bond UM, Yario TA, Steitz JA. Multiple processing-defective mutations in a mammalian histone pre-mRNA are suppressed by compensatory changes in U7 RNA both in vivo and in vitro. Genes & Development 1991, 5: 1709-1722. PMID: 1885007, DOI: 10.1101/gad.5.9.1709.Peer-Reviewed Original ResearchConceptsHistone downstream elementHistone pre-mRNAMammalian histone pre-mRNAsPre-mRNAHeLa cellsBase pair regionMammalian histonesU7 geneSm snRNPsU7 snRNPGenetic evidenceU7 snRNAUnexpected toleranceU7 RNANuclear extractsDownstream elementsSuppressor geneCompensatory changesGenesBlock substitutionsRNAVivoSnRNPsSnRNPCells
1989
The RNA binding protein La influences both the accuracy and the efficiency of RNA polymerase III transcription in vitro.
Gottlieb E, Steitz JA. The RNA binding protein La influences both the accuracy and the efficiency of RNA polymerase III transcription in vitro. The EMBO Journal 1989, 8: 841-850. PMID: 2498086, PMCID: PMC400883, DOI: 10.1002/j.1460-2075.1989.tb03445.x.Peer-Reviewed Original ResearchConceptsTranscription levelsNascent RNA polymerase III transcriptsRNA polymerase III transcriptionAbundant nuclear phosphoproteinRNA polymerase III transcriptsPolymerase III transcriptionPolymerase III transcriptsClass III genesHeLa cell extractsAction of LaTranscript lengthTermination signalNuclear phosphoproteinUridylate residuesLa proteinTranscription activityAutoantigen LaCell extractsTranscriptsRNAAbsence of LAMouse monoclonal antibodyTranscriptionPhosphoproteinGenes
1988
Four novel U RNAs are encoded by a herpesvirus
Lee S, Murthy S, Trimble J, Desrosiers R, Steitz J. Four novel U RNAs are encoded by a herpesvirus. Cell 1988, 54: 599-607. PMID: 2842058, DOI: 10.1016/s0092-8674(88)80004-7.Peer-Reviewed Original ResearchConceptsHSUR 1U RNAU RNA genesTrimethylguanosine cap structureSmall nuclear ribonucleoproteinEnd formation signalsAAUAAA polyadenylation signalBase pairing interactionsRNA genesMarmoset T lymphocytesPolyadenylation signalNuclear ribonucleoproteinCap structureEnd sequencesPerfect complementarityViral genesSnRNP particlesLow abundanceHerpesvirus saimiriRNASm determinantsGenesFormation signalEnd regionSequence
1987
Accurate 5' splice-site selection in mouse kappa immunoglobulin light chain premessenger RNAs is not cell-type-specific.
Kedes DH, Steitz JA. Accurate 5' splice-site selection in mouse kappa immunoglobulin light chain premessenger RNAs is not cell-type-specific. Proceedings Of The National Academy Of Sciences Of The United States Of America 1987, 84: 7928-7932. PMID: 3120179, PMCID: PMC299449, DOI: 10.1073/pnas.84.22.7928.Peer-Reviewed Original ResearchConceptsSplice site selectionSplice siteHeLa cellsLight chain transcriptsChain transcriptsV-J recombinationMouse kappa light chainsSplicing machineryPremessenger RNAConstant exonsGene sequencesKappa-producing cellsSynthetic transcriptsGene expressionNuclear extractsMouse B lymphocytesUpstream sitesTranscriptsExonsSequenceLight chainCellsPotential mechanismsSitesGenes