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 playTranscriptionRNAProteinMRNAHostProductionHallmark
2014
Virus Meets Host MicroRNA: the Destroyer, the Booster, the Hijacker
Guo YE, Steitz JA. Virus Meets Host MicroRNA: the Destroyer, the Booster, the Hijacker. Molecular And Cellular Biology 2014, 34: 3780-3787. PMID: 25047834, PMCID: PMC4187717, DOI: 10.1128/mcb.00871-14.Peer-Reviewed Original ResearchConceptsKey regulatory stepSmall noncoding RNAsVirus-host interactionsViral life cycleNoncoding RNAsCellular miRNAsMiRNA interactionsRegulatory stepGene expressionProtein productionHost microRNAsRNA virusesRecent discoveryLife cycleMicroRNAsMiRNAsRNADNAMRNAVirusExpressionInteractionMinireviewDiscovery
2013
The “Observer Effect” in Genome-wide Surveys of Protein-RNA Interactions
Riley KJ, Steitz JA. The “Observer Effect” in Genome-wide Surveys of Protein-RNA Interactions. Molecular Cell 2013, 49: 601-604. PMID: 23438856, PMCID: PMC3719848, DOI: 10.1016/j.molcel.2013.01.030.Peer-Reviewed Original Research
2012
Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay
Alexandrov A, Colognori D, Shu MD, Steitz JA. Human spliceosomal protein CWC22 plays a role in coupling splicing to exon junction complex deposition and nonsense-mediated decay. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 21313-21318. PMID: 23236153, PMCID: PMC3535618, DOI: 10.1073/pnas.1219725110.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCarrier ProteinsEukaryotic Initiation Factor-4AEukaryotic Initiation Factor-4GExonsGene Knockdown TechniquesHEK293 CellsHeLa CellsHumansMolecular Sequence DataMutationNonsense Mediated mRNA DecayNuclear ProteinsPeptidylprolyl IsomeraseProtein BindingRNA SplicingRNA, MessengerRNA-Binding ProteinsSpliceosomesConceptsExon junction complexEJC depositionMultiprotein exon junction complexNonsense-mediated decay pathwayNonsense-mediated decaySpecific roleEJC assemblyEJC formationComplex eukaryotesDisrupts associationMetazoan mRNAsSpliceosomal proteinsCellular mRNAsHost genesSplicing defectsJunction complexDownstream eventsSplicingNatural substrateDecay pathwaysCWC22Depletion yieldsNMDMutationsMRNA
2008
Flexibility in the site of exon junction complex deposition revealed by functional group and RNA secondary structure alterations in the splicing substrate
Mishler DM, Christ AB, Steitz JA. Flexibility in the site of exon junction complex deposition revealed by functional group and RNA secondary structure alterations in the splicing substrate. RNA 2008, 14: 2657-2670. PMID: 18952819, PMCID: PMC2590960, DOI: 10.1261/rna.1312808.Peer-Reviewed Original ResearchConceptsExon junction complexRNA secondary structureEJC depositionSplicing substrateMammalian nonsense-mediated mRNA decayNonsense-mediated mRNA decaySecondary structureStretches of DNATranslational regulationMRNA decayCoimmunoprecipitation assaysJunction complexSecondary structure alterationsDNA nucleotidesStructure alterationsH protectionUpstream shiftToeprintingExonsSitesNucleotidesDNACrystal structureDeposition sitesMRNAConserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3′‐end maturation
Kolev NG, Yario TA, Benson E, Steitz JA. Conserved motifs in both CPSF73 and CPSF100 are required to assemble the active endonuclease for histone mRNA 3′‐end maturation. EMBO Reports 2008, 9: 1013-1018. PMID: 18688255, PMCID: PMC2572124, DOI: 10.1038/embor.2008.146.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceBase SequenceCell LineCleavage And Polyadenylation Specificity FactorConserved SequenceEndonucleasesEnzyme ActivationHeLa CellsHistonesHumansMolecular Sequence DataProtein Structure, TertiaryProtein SubunitsRNA 3' End ProcessingRNA PrecursorsRNA, MessengerConceptsPre-messenger RNAPolyadenylation specificity factorMammalian proteinsRNase ZConserved motifsHistone mRNASpecificity factorEndonucleolytic cleavageActive endonucleaseEndonuclease activityMBL familyComplex machineryMessenger RNAPoint mutationsCPSF73CPSF100Process of maturationMaturation processRNAProteinMotifMRNAMaturationEukaryotesCleavage
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, MessengerRNA-Binding ProteinsTransfectionTumor 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 mRNAMRNARegulationActivationArrestMicroRNPs
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 hybridization
2005
Symplekin and multiple other polyadenylation factors participate in 3′-end maturation of histone mRNAs
Kolev NG, Steitz JA. Symplekin and multiple other polyadenylation factors participate in 3′-end maturation of histone mRNAs. Genes & Development 2005, 19: 2583-2592. PMID: 16230528, PMCID: PMC1276732, DOI: 10.1101/gad.1371105.Peer-Reviewed Original ResearchConceptsTail elongationU7 small nuclear ribonucleoproteinCommon molecular machineryMammalian cell extractsCleavage stimulation factorPolyadenylation specificity factorSmall nuclear ribonucleoproteinMolecular machineryHistone mRNAProtein complexesMRNA cleavageSpecificity factorPolyadenylation factorsTranslational activationNuclear ribonucleoproteinSymplekinReconstitution experimentsCell extractsHeat-labile factorMessenger RNAHistonesMRNAStimulation factorSubunitsCytoplasmic
2004
A molecular link between SR protein dephosphorylation and mRNA export
Huang Y, Yario TA, Steitz JA. A molecular link between SR protein dephosphorylation and mRNA export. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 9666-9670. PMID: 15210956, PMCID: PMC470732, DOI: 10.1073/pnas.0403533101.Peer-Reviewed Original ResearchConceptsNuclear export factor 1Multiple RNA-binding proteinsMRNA-protein complexesSR protein dephosphorylationMRNA nuclear exportASF/SF2RNA-binding proteinMRNA exportProtein dephosphorylationProtein complexesProtein adaptersNuclear exportSpliced mRNAPhosphorylation stateMolecular linkFactor 1MRNAHigh affinityMetazoansDephosphorylationExportComplexesSerineAdapterProteinThe Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells
Cook HL, Mischo HE, Steitz JA. The Herpesvirus saimiri Small Nuclear RNAs Recruit AU-Rich Element-Binding Proteins but Do Not Alter Host AU-Rich Element-Containing mRNA Levels in Virally Transformed T Cells. Molecular And Cellular Biology 2004, 24: 4522-4533. PMID: 15121869, PMCID: PMC400482, DOI: 10.1128/mcb.24.10.4522-4533.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceBase CompositionBase SequenceCallithrixCell LineCell Transformation, ViralELAV ProteinsELAV-Like Protein 1Herpesvirus 2, SaimiriineHeterogeneous-Nuclear Ribonucleoprotein DIn Vitro TechniquesMolecular Sequence DataMutationNucleic Acid ConformationProtein BindingRNA-Binding ProteinsRNA, MessengerRNA, Small NuclearRNA, ViralT-LymphocytesConceptsAU-rich elementsSmall nuclear RNAHSURs 1Herpesvirus saimiriNuclear RNAMRNA decay pathwayMarmoset T cellsHSUR 1HnRNP DPosttranscriptional regulationHost mRNAsHost proteinsMicroarray analysisUnknown functionProtein tristetraprolinVivo interactionDecay pathwaysHSURsMRNARNAMRNA levelsT cellsProteinCellsPathway
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
2001
Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1
Lykke-Andersen J, Shu M, Steitz J. Communication of the Position of Exon-Exon Junctions to the mRNA Surveillance Machinery by the Protein RNPS1. Science 2001, 293: 1836-1839. PMID: 11546874, DOI: 10.1126/science.1062786.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAnimalsCell LineDNA-Binding ProteinsExonsFungal ProteinsGlobinsHeLa CellsHumansMacromolecular SubstancesMiceModels, BiologicalPrecipitin TestsProtein BindingRecombinant Fusion ProteinsRibonucleoproteinsRNA HelicasesRNA SplicingRNA, MessengerRNA-Binding ProteinsSaccharomyces cerevisiae ProteinsTrans-ActivatorsTransfectionConceptsNonsense-mediated decayExon-exon junctionsMRNA surveillanceMRNA quality controlMRNA surveillance machinerySelective nuclear exportBeta-globin mRNAPremature termination codonUpf complexMature mRNASurveillance machineryNuclear exportAberrant mRNAsMammalian cellsTermination codonUntranslated regionSplice junctionsRNPS1MRNADual roleCentral componentComplexesCodonSubunitsMachinery
2000
Human Upf Proteins Target an mRNA for Nonsense-Mediated Decay When Bound Downstream of a Termination Codon
Lykke-Andersen J, Shu M, Steitz J. Human Upf Proteins Target an mRNA for Nonsense-Mediated Decay When Bound Downstream of a Termination Codon. Cell 2000, 103: 1121-1131. PMID: 11163187, DOI: 10.1016/s0092-8674(00)00214-2.Peer-Reviewed Original ResearchConceptsNonsense-mediated decayExon-exon junctionsTermination codonMRNA exon-exon junctionsNovel human proteinTranslation termination siteHeLa cell extractsBeta-globin mRNAPremature termination codonUpf proteinsEukaryotic cellsAberrant mRNAsHuman proteinsTermination sitesIntact cellsCell extractsCodonHUpf2ProteinMRNAHUpf1CellsCytoplasmCytoplasmicTethering
1998
HNS, a nuclear-cytoplasmic shuttling sequence in HuR
Fan X, Steitz J. HNS, a nuclear-cytoplasmic shuttling sequence in HuR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 15293-15298. PMID: 9860962, PMCID: PMC28036, DOI: 10.1073/pnas.95.26.15293.Peer-Reviewed Original ResearchMeSH Keywords3T3 CellsAmino Acid SequenceAnimalsAntigens, SurfaceCell NucleusConserved SequenceCytoplasmELAV ProteinsELAV-Like Protein 1HeLa CellsHeterogeneous-Nuclear Ribonucleoprotein KHumansMiceMolecular Sequence DataRecombinant ProteinsRibonucleoproteinsRNA, MessengerRNA-Binding ProteinsSequence AlignmentSequence Homology, Amino AcidTransfectionXenopusConceptsHeterogeneous nuclear ribonucleoprotein KNuclear localization signal activityClassical nuclear localization signalAU-rich element-containing mRNAsExport of mRNAHeterogeneous nuclear ribonucleoprotein A1Nuclear export signalNuclear localization signalNuclear transport processRNA-binding proteinAU-rich elementsExport signalLocalization signalM9 sequenceNuclear poresDomain sequencesCytoplasmic compartmentUntranslated regionLabile mRNAsCell nucleiSpecific signalsHuRProteinBidirectional transportMRNAAUUUA Sequences Direct mRNA Deadenylation Uncoupled from Decay during Xenopus Early Development
Voeltz G, Steitz J. AUUUA Sequences Direct mRNA Deadenylation Uncoupled from Decay during Xenopus Early Development. Molecular And Cellular Biology 1998, 18: 7537-7545. PMID: 9819439, PMCID: PMC109334, DOI: 10.1128/mcb.18.12.7537.Peer-Reviewed Original ResearchConceptsAU-rich elementsXenopus early developmentGranulocyte-macrophage colony-stimulating factor (GM-CSF) geneUntranslated region sequencesHuman granulocyte-macrophage colony-stimulating factor geneChimeric mRNAMid-blastula transitionEarly developmentColony-stimulating factor geneRNA deadenylationMRNA decayRapid deadenylationMRNA deadenylationDeadenylation activityDeadenylationFactor genesRegion sequencesEgg activationAUUUAC-MycMature eggsXenopus oocytesMRNAOocytesXenopus
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 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
1996
Length suppression in histone messenger RNA 3′-end maturation: Processing defects of insertion mutant premessenger RNAs can be compensated by insertions into the U7 small nuclear RNA
Scharl E, Steitz J. Length suppression in histone messenger RNA 3′-end maturation: Processing defects of insertion mutant premessenger RNAs can be compensated by insertions into the U7 small nuclear RNA. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 14659-14664. PMID: 8962110, PMCID: PMC26191, DOI: 10.1073/pnas.93.25.14659.Peer-Reviewed Original ResearchConceptsHistone downstream elementU7 RNAHistone messenger RNASmall nuclear RNARNA processing systemSmall ribonucleoproteinPremessenger RNANuclear RNAPre-mRNAU7 small nuclear RNADownstream elementsCleavage siteRNAMessenger RNAXenopus oocytesBase pairingProcessing defectsU7First demonstrationHistonesRNAsRibonucleoproteinInsertionMRNASites
1977
Characterization of two mRNA · rRNA complexes implicated in the initiation of protein biosynthesis
Steitz J, Steege D. Characterization of two mRNA · rRNA complexes implicated in the initiation of protein biosynthesis. Journal Of Molecular Biology 1977, 114: 545-558. PMID: 335077, DOI: 10.1016/0022-2836(77)90177-2.Peer-Reviewed Original ResearchConceptsProtein biosynthesisEscherichia coli 16 S ribosomal RNAS ribosomal RNABase pair regionNuclease digestion studiesFragment complexAssignment of residuesRibosomal RNARRNA complexLambda PRBacteriophage lambdaMolecular understandingInitiation siteInitiation eventsStrong experimental supportMessenger RNABiosynthesisThermal denaturation studiesDenaturation studiesRNAPR transcriptsPR regionDigestion studiesMRNAComplexes