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
2016
Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation
Alexandrov A, Shu MD, Steitz JA. Fluorescence Amplification Method for Forward Genetic Discovery of Factors in Human mRNA Degradation. Molecular Cell 2016, 65: 191-201. PMID: 28017590, PMCID: PMC5301997, DOI: 10.1016/j.molcel.2016.11.032.Peer-Reviewed Original ResearchConceptsNonsense-mediated decayPremature termination codonNMD factorsNMD pathwayMRNA degradationHuman cellsForward genetic screeningGenetic screen identifiesHuman genetic diseasesHuman candidate genesNonsense suppression therapyModel organismsGenetic screeningScreen identifiesTermination codonCandidate genesGenetic discoveriesReporter fluorescenceGenetic diseasesPathwayAdditional key factorsCellsCRISPRCodonHomology
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
2011
Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex
Alexandrov A, Colognori D, Steitz JA. Human eIF4AIII interacts with an eIF4G-like partner, NOM1, revealing an evolutionarily conserved function outside the exon junction complex. Genes & Development 2011, 25: 1078-1090. PMID: 21576267, PMCID: PMC3093123, DOI: 10.1101/gad.2045411.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsDEAD-box RNA HelicasesEukaryotic Initiation Factor-4AEukaryotic Initiation Factor-4GEvolution, MolecularExonsGene DeletionGenetic Complementation TestHumansModels, MolecularMolecular Sequence DataMutationNuclear ProteinsPhenotypeProtein Structure, TertiaryRNA, Ribosomal, 18SRNA-Binding ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentConceptsExon junction complexEIF4GJunction complexDEAD-box helicasePre-rRNA processingDirect physical interactionEIF4G complexExtragenic suppressorsBiogenesis defectsLethal phenotypeGrowth defectTranslation initiationHuman orthologEIF4AIIISaccharomyces cerevisiaeHuman cellsNOM1Physical interactionComplex actsG complexX-ray structureMutationsResiduesComplexesOrthologs
2010
miR-29 and miR-30 regulate B-Myb expression during cellular senescence
Martinez I, Cazalla D, Almstead LL, Steitz JA, DiMaio D. miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 108: 522-527. PMID: 21187425, PMCID: PMC3021067, DOI: 10.1073/pnas.1017346108.Peer-Reviewed Original ResearchConceptsB-myb expressionCellular senescenceMiR-30MiR-29Reporter constructsEndogenous B-MybMajor tumor suppressor mechanismTumor suppressor mechanismIrreversible growth arrestMicroRNA familiesMutant 3'UTRCellular DNA synthesisB-MybReplicative senescenceCompensatory mutationsGrowth arrestMutant sitesRb pathwaySenescenceSuppressor mechanismDNA synthesisRepressionInhibits senescenceExpressionMutationsPoly(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
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
2004
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
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, MessengerRNA, Small NuclearRNA, ViralRNA-Binding ProteinsT-LymphocytesConceptsAU-rich elementsSmall nuclear RNAHSURs 1Herpesvirus saimiriNuclear RNAMRNA decay pathwayMarmoset T cellsHSUR 1HnRNP DPosttranscriptional regulationHost mRNAsHost proteinsMicroarray analysisUnknown functionProtein tristetraprolinVivo interactionDecay pathwaysHSURsMRNARNAMRNA levelsT cellsProteinCellsPathwayTransportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR
Rebane A, Aab A, Steitz JA. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. RNA 2004, 10: 590-599. PMID: 15037768, PMCID: PMC1370549, DOI: 10.1261/rna.5224304.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAmino Acid SequenceAntigens, SurfaceBeta KaryopherinsCell NucleusELAV ProteinsELAV-Like Protein 1HeLa CellsHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHumansMolecular Sequence DataMutationProtein Structure, TertiaryRan GTP-Binding ProteinReceptors, Cytoplasmic and NuclearRNA-Binding ProteinsSequence Analysis, ProteinConceptsHnRNP A1Transportin-1Import factorsDigitonin-permeabilized HeLa cellsNuclear import factorsMRNA-binding proteinRecombinant hnRNP A1Binding of HuRImp betaImport pathwayCargo specificityNuclear importExport receptorTransportin-2TransportinTransport signalHeLa cellsLikely actsHuRTrn1ProteinInteraction studiesImportTRN2RanGTP
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 activityDeadenylationSnRNAMachineryProteinDegradation
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
1994
Sequence and structural elements critical for U8 snRNP function in Xenopus oocytes are evolutionarily conserved.
Peculis BA, Steitz JA. Sequence and structural elements critical for U8 snRNP function in Xenopus oocytes are evolutionarily conserved. Genes & Development 1994, 8: 2241-2255. PMID: 7958892, DOI: 10.1101/gad.8.18.2241.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBiological EvolutionChromosomal Proteins, Non-HistoneConserved SequenceFemaleMethylationMolecular Sequence DataMutagenesis, Site-DirectedMutationNucleic Acid ConformationOocytesRibonucleoproteins, Small NuclearRNA CapsRNA PrecursorsRNA Processing, Post-TranscriptionalRNA, Small NuclearXenopus
1993
Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic 5′ splice sites in vivo.
Cortes JJ, Sontheimer EJ, Seiwert SD, Steitz JA. Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic 5′ splice sites in vivo. The EMBO Journal 1993, 12: 5181-5189. PMID: 8262061, PMCID: PMC413781, DOI: 10.1002/j.1460-2075.1993.tb06213.x.Peer-Reviewed Original ResearchConceptsSplice siteRabbit beta-globin geneBeta-globin transcriptsBeta-globin geneU5 genesConserved loopMRNA splicingU5 snRNASecond intronFirst exonExon sequencesLoop mutantsSecond exonExpression vectorTransient transfectionCryptic sitesNovel siteHeLa cellsGT dinucleotideExonsExon 1U5 sequencesSnRNAMutationsVivo system
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
Each of the conserved sequence elements flanking the cleavage site of mammalian histone pre-mRNAs has a distinct role in the 3'-end processing reaction.
Mowry KL, Oh R, Steitz JA. Each of the conserved sequence elements flanking the cleavage site of mammalian histone pre-mRNAs has a distinct role in the 3'-end processing reaction. Molecular And Cellular Biology 1989, 9: 3105-3108. PMID: 2779556, PMCID: PMC362782, DOI: 10.1128/mcb.9.7.3105.Peer-Reviewed Original Research
1987
Recognition of mutant and cryptic 5' splice sites by the U1 small nuclear ribonucleoprotein in vitro.
Chabot B, Steitz JA. Recognition of mutant and cryptic 5' splice sites by the U1 small nuclear ribonucleoprotein in vitro. Molecular And Cellular Biology 1987, 7: 698-707. PMID: 2950313, PMCID: PMC365126, DOI: 10.1128/mcb.7.2.698.Peer-Reviewed Original ResearchMultiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes.
Chabot B, Steitz JA. Multiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes. Molecular And Cellular Biology 1987, 7: 281-293. PMID: 2951586, PMCID: PMC365068, DOI: 10.1128/mcb.7.1.281.Peer-Reviewed Original Research
1983
RNA processing: Lessons from mutant globins
Mount S, Steitz J. RNA processing: Lessons from mutant globins. Nature 1983, 303: 380-381. PMID: 6855891, DOI: 10.1038/303380a0.Peer-Reviewed Original Research
1979
Binding of mammalian ribosomes to ms2 phage rna reveals an overlapping gene encoding a lysis function
Atkins J, Steitz J, Anderson C, Model P. Binding of mammalian ribosomes to ms2 phage rna reveals an overlapping gene encoding a lysis function. Cell 1979, 18: 247-256. PMID: 498271, DOI: 10.1016/0092-8674(79)90044-8.Peer-Reviewed Original ResearchConceptsMammalian ribosomesLysis functionE. coli cell-free systemAmino acid polypeptideCoat protein geneAmino acid sequence analysisPartial amino acid sequence analysisMS2 phage RNAAcid sequence analysisCell-free systemLysis genesNonsense mutantsSynthetase geneUAA codonProtein geneAcid polypeptideSite mutantsTranslation productsInitiator regionSecond codonCistronNonpermissive cellsSame proteinPhage RNAAUG triplet