2024
Emerging and re-emerging themes in co-transcriptional pre-mRNA splicing
Carrocci T, Neugebauer K. Emerging and re-emerging themes in co-transcriptional pre-mRNA splicing. Molecular Cell 2024, 84: 3656-3666. PMID: 39366353, PMCID: PMC11463726, DOI: 10.1016/j.molcel.2024.08.036.Peer-Reviewed Original ResearchConceptsPre-mRNA splicingCo-transcriptional pre-mRNA splicingCo-transcriptional RNA foldingCo-transcriptional processesRNA polymerase IIPre-messenger RNAFunctional messenger RNAsCapping enzymePolymerase IIDelayed splicingPolyadenylation machinerySplicing eventsPre-mRNAGene regulationMacromolecular machinesRNA foldingRNA synthesisMRNA isoformsProtein productionGene expressionSplicingRNARegulatory importanceCross-regulationMessenger RNA
2021
Modulation of RNA Splicing Enhances Response to BCL2 Inhibition in Acute Myeloid Leukemia
Wang E, Pineda J, Bourcier J, Stahl M, Penson A, Wakiro I, Singer M, Cui D, Erickson C, Knorr K, Stanley R, Chen X, McMillan E, Bossard C, Aifantis I, Bradley R, Abdel-Wahab O. Modulation of RNA Splicing Enhances Response to BCL2 Inhibition in Acute Myeloid Leukemia. Blood 2021, 138: 507. DOI: 10.1182/blood-2021-146373.Peer-Reviewed Original ResearchCdc2-like kinasePre-mRNA splicingRNA splicing factorsSplicing factorsRNA processingAcute myeloid leukemiaRNA splicingBCL2 inhibitionGenetic screeningPhosphorylation of splicing factorsRegulate pre-mRNA splicingModulates RNA splicingSR protein functionResistance to therapyAntiapoptotic protein Bcl-2Overcome venetoclax resistanceRNA processing factorsDrug responseAML drugsGenome-wide CRISPR/Cas9 screenEntity's Board of DirectorsDrug-gene interactionsProtein Bcl-2Treated AML cellsAnti-apoptotic factors
2013
The nuclear cap-binding complex interacts with the U4/U6·U5 tri-snRNP and promotes spliceosome assembly in mammalian cells
Pabis M, Neufeld N, Steiner MC, Bojic T, Shav-Tal Y, Neugebauer KM. The nuclear cap-binding complex interacts with the U4/U6·U5 tri-snRNP and promotes spliceosome assembly in mammalian cells. RNA 2013, 19: 1054-1063. PMID: 23793891, PMCID: PMC3708526, DOI: 10.1261/rna.037069.112.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesGenes, fosGuanosineHeLa CellsHumansModels, BiologicalNuclear Cap-Binding Protein ComplexProtein Interaction Domains and MotifsRibonucleoprotein, U1 Small NuclearRibonucleoprotein, U4-U6 Small NuclearRibonucleoprotein, U5 Small NuclearRNA InterferenceRNA PrecursorsRNA SplicingSpliceosomesConceptsCap-binding complexCotranscriptional spliceosome assemblyU4/Spliceosome assemblySpliceosomal snRNPsRNA polymerase II transcriptsNuclear cap-binding complexPolymerase II transcriptsRecruitment of U1RNA-independent fashionActive transcription unitsPre-mRNA splicingLive-cell imaging assaysNonsense-mediated decayNetwork of interactionsRNA biogenesisGuanosine capSnRNP biogenesisMiRNA biogenesisTri-snRNPSnRNA exportSnRNP proteinsTranscription unitChromatin immunoprecipitationMammalian cells
2012
A Dual Role of Evi-1 During Developmental Hematopoiesis
Konantz M, Grauer M, Grzywna S, Park I, Daley G, Kanz L, Lengerke C. A Dual Role of Evi-1 During Developmental Hematopoiesis. Blood 2012, 120: 765. DOI: 10.1182/blood.v120.21.765.765.Peer-Reviewed Original ResearchEvi-1Developmental hematopoiesisZebrafish embryosSCL expressionProgenitor cellsHematopoietic cellsPre-mRNA splicingHuman hematopoietic developmentEvi-1 locusMurine hematopoietic cellsHuman iPS cellsPrecise molecular basisSurvival/proliferationEmbryonic myelopoiesisPluripotent stem cellsEvi-1 expressionErythroid progenitor cellsDefinitive hematopoiesisPrimitive erythroid progenitor cellsPrimitive erythropoiesisZebrafish zygotesHSC formationPrimitive hematopoiesisBlood developmentSitu hybridization analysis
2011
Evi-1 Regulates Myelopoiesis and Hematopoietic Stem Cell Development in Zebrafish and Human Pluripotent Stem Cells
Konantz M, Grauer M, Grzywna S, Brugman M, Kanz L, Park I, Daley G, Baum C, Lengerke C. Evi-1 Regulates Myelopoiesis and Hematopoietic Stem Cell Development in Zebrafish and Human Pluripotent Stem Cells. Blood 2011, 118: 1281. DOI: 10.1182/blood.v118.21.1281.1281.Peer-Reviewed Original ResearchHuman pluripotent stem cellsPluripotent stem cellsEvi-1Developmental hematopoiesisZebrafish embryosHematopoietic developmentHematopoietic stem cellsStem cellsPosterior lateral plate mesodermHematopoietic stem cell developmentPosterior blood islandHuman developmental hematopoiesisLateral plate mesodermStem cell developmentPre-mRNA splicingEvi-1 locusDays post fertilizationHematopoietic stem cell proliferationMurine hematopoietic cellsStem cell proliferationExpression of PUEmbryonic myelopoiesisEvi-1 expressionErythroid progenitor cellsPrimitive erythroid progenitor cellsCotranscriptional spliceosome assembly and splicing are independent of the Prp40p WW domain
Görnemann J, Barrandon C, Hujer K, Rutz B, Rigaut G, Kotovic KM, Faux C, Neugebauer KM, Séraphin B. Cotranscriptional spliceosome assembly and splicing are independent of the Prp40p WW domain. RNA 2011, 17: 2119-2129. PMID: 22020974, PMCID: PMC3222125, DOI: 10.1261/rna.02646811.Peer-Reviewed Original ResearchConceptsC-terminal domainWW domainsSpliceosome assemblyU1 snRNPPol II C-terminal domainCotranscriptional spliceosome assemblyComplex cellular functionsRNA polymerase IIProtein-protein interactionsPre-mRNA splicingU2 snRNP recruitmentSplice site recognitionCotranscriptional recruitmentTranscriptional machineryPolymerase IIPol IIU5 snRNPLarge subunitSplicing factorsCellular functionsStable heterodimerComplex assemblyPrp40Spliceosome formationAffinity purificationPause locally, splice globally
Oesterreich F, Bieberstein N, Neugebauer KM. Pause locally, splice globally. Trends In Cell Biology 2011, 21: 328-335. PMID: 21530266, DOI: 10.1016/j.tcb.2011.03.002.Peer-Reviewed Original ResearchConceptsRNA polymerase II elongation rateContext of chromatinProtein-coding transcriptsRNA polymerase IIPre-mRNA splicingTranscript bodyTranscriptional pausingHistone modificationsPolymerase IIIntron removalSplicingTranscriptionElongation rateGenesTranscriptsRecent evidenceChromatinIntronsPausingElongationRegulatorLocal regulationRegulationRecruitment
2010
Global Analysis of Nascent RNA Reveals Transcriptional Pausing in Terminal Exons
Oesterreich F, Preibisch S, Neugebauer KM. Global Analysis of Nascent RNA Reveals Transcriptional Pausing in Terminal Exons. Molecular Cell 2010, 40: 571-581. PMID: 21095587, DOI: 10.1016/j.molcel.2010.11.004.Peer-Reviewed Original ResearchConceptsTerminal exonNascent RNATranscription profilesIntron-containing genesHigh-density tiling microarraysPre-mRNA splicingSplicing kineticsTranscriptional pausingTiling microarraysPol IISplicing catalysisSplicing efficiencyGenes lackSplicingExonsTranscriptionGenesRNAGlobal analysisFunctional couplingSilico simulationsIntronlessSpliceosomePausingYeast
2009
The Zebrafish Homologue of the Murine Ecotropic Viral Integration Site-1 (. Evi-1) gene Regulates Zebrafish Embryonic Blood Development.
Konantz M, Brugman M, Park I, Daley G, Nuesslein-Volhard C, Baum C, Lengerke C. The Zebrafish Homologue of the Murine Ecotropic Viral Integration Site-1 (. Evi-1) gene Regulates Zebrafish Embryonic Blood Development. Blood 2009, 114: 1461. DOI: 10.1182/blood.v114.22.1461.1461.Peer-Reviewed Original ResearchZebrafish embryonic developmentBlood developmentEvi-1Embryonic hematopoiesisEmbryonic developmentPluripotent stem cellsGATA1 expressionHematopoietic developmentPosterior lateral plate mesodermPosterior blood islandWild-type embryosMorpholino-injected embryosLateral plate mesodermPre-mRNA splicingStem cellsSomite stage embryosAdult hematopoietic cellsHuman pluripotent stem cellsReal-time PCR analysisHematopoietic stem cell proliferationHuman blood developmentStem cell proliferationHuman iPS cellsZebrafish homologueErythroid progenitor cells
2005
Autoantibody Recognition of Macromolecular Structures and Their Subunits
Champion E, Baserga S. Autoantibody Recognition of Macromolecular Structures and Their Subunits. 2005, 379-417. DOI: 10.1002/3527607854.ch17.Peer-Reviewed Original ResearchSm monoclonal antibodyRNA polymerase IBox C/D small nucleolar RNAsPre-mRNA splicingRNase MRPSmall nucleolar RNAsRNase PPolymerase IU3 snoRNASubcellular localizationMolecular markersProtein componentsNucleolar RNAsHuman exosomeNew functionsPolymyositis-scleroderma overlap syndromeCurrent understandingSnRNPsSnoRNAsSplicingFibrillarinNucleolarMonoclonal antibodiesExosomesHUBF
2002
The Divergent U12-Type Spliceosome Is Required for Pre-mRNA Splicing and Is Essential for Development in Drosophila
Otake LR, Scamborova P, Hashimoto C, Steitz JA. The Divergent U12-Type Spliceosome Is Required for Pre-mRNA Splicing and Is Essential for Development in Drosophila. Molecular Cell 2002, 9: 439-446. PMID: 11864616, DOI: 10.1016/s1097-2765(02)00441-0.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAnimals, Genetically ModifiedBase SequenceDrosophila melanogasterDrosophila ProteinsGenes, LethalIntronsLarvaMolecular Sequence DataMutagenesis, InsertionalNerve Tissue ProteinsNuclear ProteinsNucleic Acid ConformationProtein IsoformsRibonucleoprotein, U4-U6 Small NuclearRibonucleoproteins, Small NuclearRNA PrecursorsRNA SplicingRNA, Small NuclearSequence AlignmentSequence Homology, Nucleic AcidSpliceosomesTranscription FactorsTransgenesConceptsU12-type spliceosomeThird instar larvalU12-type intronsPre-mRNA splicingU4atac/U6atacMetazoan organismsHomeodomain proteinsU5 snRNPsDrosophila melanogasterU12 spliceosomeMRNA intronsU12 snRNASingle locusU6atacInstar larvalSpliceosomeEmbryonic stagesCNS developmentIntronsMinor classU12DrosophilaMelanogasterVertebratesSnRNPs
1998
Modifications of U2 snRNA are required for snRNP assembly and pre‐mRNA splicing
Yu Y, Shu M, Steitz J. Modifications of U2 snRNA are required for snRNP assembly and pre‐mRNA splicing. The EMBO Journal 1998, 17: 5783-5795. PMID: 9755178, PMCID: PMC1170906, DOI: 10.1093/emboj/17.19.5783.Peer-Reviewed Original ResearchConceptsEnd of U2Native gel analysisPre-mRNA splicingU2 snRNP particleGlycerol gradient analysisPseudouridylation activityGuanosine capSnRNP assemblySpliceosomal snRNAsSplicing activityTMG capSpliceosome assemblyU2 RNAU2 snRNAU2 functionProtein profilesGel analysisSnRNP particlesXenopus oocytesInternal modificationSnRNASplicingPotent inhibitorU2Extensive modification
1997
Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription.
Neugebauer K, Roth M. Distribution of pre-mRNA splicing factors at sites of RNA polymerase II transcription. Genes & Development 1997, 11: 1148-1159. PMID: 9159396, DOI: 10.1101/gad.11.9.1148.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalBinding SitesCell NucleusFluorescent Antibody Technique, IndirectHeLa CellsHumansNuclear ProteinsPhosphoproteinsRibonucleoproteins, Small NuclearRNA Polymerase IIRNA PrecursorsRNA SplicingRNA-Binding ProteinsSerine-Arginine Splicing FactorsTranscription, GeneticUridine TriphosphateConceptsRNA polymerase II transcriptionPolymerase II transcriptionMRNA splicing factorsSplicing factorsSR familyPre-mRNA splicingVisualization of hundredsHeLa cell nucleiSplicing regulatorsActive genesTranscription unitMRNA splicingGene regulatorsGene transcriptionPre-mRNADistinct functionsRNA synthesisTranscriptionCell nucleiSplicingSingle memberRegulatorActive site
1993
Distinct Functions of SR Proteins in Alternative pre-mRNA Splicing
Zahler A, Neugebauer K, Lane W, Roth M. Distinct Functions of SR Proteins in Alternative pre-mRNA Splicing. Science 1993, 260: 219-222. PMID: 8385799, DOI: 10.1126/science.8385799.Peer-Reviewed Original ResearchConceptsSR proteinsAlternative splicingDistinct functionsAlternative pre-mRNA splicingPrecursor messenger RNAMRNA splicing factorsPre-mRNA splicingSR familySplicing factorsMRNA splicingVariety of tissuesGene expressionSplicingMessenger RNAProteinCommon mechanismFundamental roleFamilyRNARegulationExpressionEntire familyFunctionMembers
1986
Pre-mRNA splicing in vitro requires intact U4/U6 small nuclear ribonucleoprotein
Black D, Steitz J. Pre-mRNA splicing in vitro requires intact U4/U6 small nuclear ribonucleoprotein. Cell 1986, 46: 697-704. PMID: 2427202, DOI: 10.1016/0092-8674(86)90345-4.Peer-Reviewed Original Research
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