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
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-Binding ProteinsRNA, MessengerSpliceosomesConceptsExon 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-Binding ProteinsRNA, Ribosomal, 18SSaccharomyces 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
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
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
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-Binding ProteinsRNA, MessengerSaccharomyces 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 componentComplexesCodonSubunitsMachineryDynamic Exchanges of RNA Interactions Leading to Catalytic Core Formation in the U12-Dependent Spliceosome
Frilander M, Steitz J. Dynamic Exchanges of RNA Interactions Leading to Catalytic Core Formation in the U12-Dependent Spliceosome. Molecular Cell 2001, 7: 217-226. PMID: 11172726, DOI: 10.1016/s1097-2765(01)00169-1.Peer-Reviewed Original Research
1996
Highly Diverged U4 and U6 Small Nuclear RNAs Required for Splicing Rare AT-AC Introns
Tarn W, Steitz J. Highly Diverged U4 and U6 Small Nuclear RNAs Required for Splicing Rare AT-AC Introns. Science 1996, 273: 1824-1832. PMID: 8791582, DOI: 10.1126/science.273.5283.1824.Peer-Reviewed Original ResearchA 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
1993
The U5 and U6 Small Nuclear RNAs as Active Site Components of the Spliceosome
Sontheimer E, Steitz J. The U5 and U6 Small Nuclear RNAs as Active Site Components of the Spliceosome. Science 1993, 262: 1989-1996. PMID: 8266094, DOI: 10.1126/science.8266094.Peer-Reviewed Original ResearchConceptsSmall nuclear RNANuclear RNAPrecursor messenger RNA splicingLariat intermediateU6 small nuclear RNAMessenger RNA splicingExon 1Self-splicing intronsActive site componentsRNA splicingMammalian spliceosomeU6 RNARNA contactsMechanistic parallelsPre-mRNAVitro splicingSubsequent splicingSplicingSpliceosomeSplice siteLast residueFirst residueFunctional interactionIntron productsRNAUncoupling two functions of the U1 small nuclear ribonucleoprotein particle during in vitro splicing.
Seiwert SD, Steitz JA. Uncoupling two functions of the U1 small nuclear ribonucleoprotein particle during in vitro splicing. Molecular And Cellular Biology 1993, 13: 3135-3145. PMID: 7684489, PMCID: PMC359749, DOI: 10.1128/mcb.13.6.3135.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsBase SequenceCaenorhabditis elegansCell NucleusExonsHeLa CellsHumansMolecular Sequence DataNucleic Acid ConformationOligodeoxyribonucleotidesPlasmidsRibonucleoprotein, U1 Small NuclearRNARNA SplicingRNA, Small NuclearSequence Homology, Nucleic AcidTranscription, GeneticTrypanosomatinaConceptsSmall nuclear ribonucleoprotein particleU1 small nuclear ribonucleoprotein particleNuclear ribonucleoprotein particleSplice site recognitionU1 snRNASL RNASplice site regionSplicing substrateRibonucleoprotein particleSpliced leader RNA sequencesVitro splicingSplice siteU1 snRNP functionsEssential splicing factorLeader RNA sequencesNative gel analysisSnRNP functionCaenorhabditis elegansSplicing complexesSplicing factorsLeptomonas collosomaSpliceosome assemblyDifferent intronsU1 RNAMethyl oligoribonucleotideAssociation with terminal exons in pre-mRNAs: a new role for the U1 snRNP?
Wassarman KM, Steitz JA. Association with terminal exons in pre-mRNAs: a new role for the U1 snRNP? Genes & Development 1993, 7: 647-659. PMID: 8384583, DOI: 10.1101/gad.7.4.647.Peer-Reviewed Original ResearchAdenoviridaeBase SequenceBinding SitesCross-Linking ReagentsDNA Mutational AnalysisExonsFurocoumarinsHeLa CellsHistonesHumansMolecular Sequence DataOligonucleotide ProbesPoly ARestriction MappingRibonucleoprotein, U1 Small NuclearRNA PrecursorsRNA Processing, Post-TranscriptionalRNA SplicingRNA, Small NuclearSimian virus 40
1992
Site-specific cross-linking of mammalian U5 snRNP to the 5' splice site before the first step of pre-mRNA splicing.
Wyatt JR, Sontheimer EJ, Steitz JA. Site-specific cross-linking of mammalian U5 snRNP to the 5' splice site before the first step of pre-mRNA splicing. Genes & Development 1992, 6: 2542-2553. PMID: 1340469, DOI: 10.1101/gad.6.12b.2542.Peer-Reviewed Original ResearchConceptsSplice siteMRNA splicingATP-dependent interactionHeLa nuclear extractsU5 snRNPMRNA substratesSplice site regionProtein factorsU5 snRNANucleotides upstreamU6 snRNAPre-mRNANuclear extractsSplicingSite regionLoop sequenceCross-link formationSnRNASplicing conditionsWatson-Crick complementarityCross-linking strategyU1Selective photoactivationSnRNPMammalian
1990
Spliced leader RNA sequences can substitute for the essential 5′ end of U1 RNA during splicing in a mammalian in vitro system
Bruzik J, Steitz J. Spliced leader RNA sequences can substitute for the essential 5′ end of U1 RNA during splicing in a mammalian in vitro system. Cell 1990, 62: 889-899. PMID: 2168293, DOI: 10.1016/0092-8674(90)90264-f.Peer-Reviewed Original Research
1987
Multiple 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