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
2023
Splicing under stress: A matter of time and place
Podszywalow-Bartnicka P, Neugebauer K. Splicing under stress: A matter of time and place. Journal Of Cell Biology 2023, 222: e202311014. PMID: 37988026, PMCID: PMC10660129, DOI: 10.1083/jcb.202311014.Peer-Reviewed Original Research
2022
Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies
Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Molecular Cell 2022, 82: 1107-1122.e7. PMID: 35303483, PMCID: PMC8988922, DOI: 10.1016/j.molcel.2022.02.025.Peer-Reviewed Original Research
2019
Uncoupling of nucleo-cytoplasmic RNA export and localization during stress
Hochberg-Laufer H, Schwed-Gross A, Neugebauer KM, Shav-Tal Y. Uncoupling of nucleo-cytoplasmic RNA export and localization during stress. Nucleic Acids Research 2019, 47: 4778-4797. PMID: 30864659, PMCID: PMC6511838, DOI: 10.1093/nar/gkz168.Peer-Reviewed Original ResearchConceptsRNA-binding proteinStress granulesNuclear specklesMRNA exportFormation of SGsCytoplasmic stress granulesSub-cellular compartmentsGene expression pathwaysMRNA export adaptorsComplex recruitmentEukaryotic cellsRNA exportRNA metabolismExport adaptorGranule assemblyNuclear proteinsExpression pathwaysRNAStress inductionMRNACytoplasmProteinPotent inhibitorCellsNucleoporins
2018
Dynamics and Function of Nuclear Bodies during Embryogenesis
Escayola D, Neugebauer K. Dynamics and Function of Nuclear Bodies during Embryogenesis. Biochemistry 2018, 57: 2462-2469. PMID: 29473743, DOI: 10.1021/acs.biochem.7b01262.Peer-Reviewed Original ResearchConceptsNuclear bodiesCajal bodiesRNA processingZygotic gene productsRNA-protein complexesEfficient RNA processingFunction of nucleoliNuclear body formationGene elementsVariety of organismsZygotic genomeZygotic transitionGenomic lociNascent RNAModel organismsNuclear stepsTranscriptional activationEarly embryosNuclear proteinsGene productsGene locusMembraneless organellesBody formationExcellent modelCell nuclei
2016
Activation of transcription enforces the formation of distinct nuclear bodies in zebrafish embryos
Heyn P, Salmonowicz H, Rodenfels J, Neugebauer KM. Activation of transcription enforces the formation of distinct nuclear bodies in zebrafish embryos. RNA Biology 2016, 14: 752-760. PMID: 27858508, PMCID: PMC5519242, DOI: 10.1080/15476286.2016.1255397.Peer-Reviewed Original ResearchConceptsHistone locus bodyCajal bodiesNuclear bodiesSm ringHistone mRNA 3' end processingEnd processingMRNA 3' end processingDifferent nuclear bodiesDistinct nuclear bodiesNuclear body componentsDistinct regulatory functionsHLB formationHistone genesHistone transcriptsZygotic transcriptionTranscriptional silenceSplicing machineryRRNA processingEarly embryogenesisU7 snRNPNascent histoneZebrafish embryosDanio rerioCellular compartmentsTranscription inhibitionSplicing of Nascent RNA Coincides with Intron Exit from RNA Polymerase II
Oesterreich F, Herzel L, Straube K, Hujer K, Howard J, Neugebauer KM. Splicing of Nascent RNA Coincides with Intron Exit from RNA Polymerase II. Cell 2016, 165: 372-381. PMID: 27020755, PMCID: PMC4826323, DOI: 10.1016/j.cell.2016.02.045.Peer-Reviewed Original ResearchConceptsRNA polymerase IIPolymerase IIPol IIProtein-coding genesPol II progressionRNA sequencing methodsGene expression pathwaysRate of transcriptionEndogenous genesSplicing catalysisSplicing profilesSpliceosome assemblyExpression pathwaysSpliced productsGene expressionIntronsSplicingSequencing methodsMechanistic insightsGenesRegulationKinetic competitionEukaryotesSpliceosomeTranscription
2015
Quantification of co-transcriptional splicing from RNA-Seq data
Herzel L, Neugebauer KM. Quantification of co-transcriptional splicing from RNA-Seq data. Methods 2015, 85: 36-43. PMID: 25929182, DOI: 10.1016/j.ymeth.2015.04.024.Peer-Reviewed Original Research
2014
Introns and gene expression: Cellular constraints, transcriptional regulation, and evolutionary consequences
Heyn P, Kalinka AT, Tomancak P, Neugebauer KM. Introns and gene expression: Cellular constraints, transcriptional regulation, and evolutionary consequences. BioEssays 2014, 37: 148-154. PMID: 25400101, PMCID: PMC4654234, DOI: 10.1002/bies.201400138.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological EvolutionCell CycleGene Expression RegulationHumansIntronsRNA SplicingConceptsShort genesCellular constraintsImportant regulatory playersRNA polymerase IICell cycle constraintsLength of exonsNumber of transcriptsShorter cell cycleEvolutionary consequencesPolymerase IITranscriptional regulationAnimal ontogenyLong genesRegulatory playersTranscript productionDifferent genesGene expressionExpression profilesCell cycleEfficient expressionIntronsGenesCell typesTiming mechanismTranscripts
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
Cajal bodies: where form meets function
Machyna M, Heyn P, Neugebauer KM. Cajal bodies: where form meets function. Wiley Interdisciplinary Reviews - RNA 2012, 4: 17-34. PMID: 23042601, DOI: 10.1002/wrna.1139.Peer-Reviewed Original ResearchConceptsCajal bodiesCB assemblyHistone locus bodyHistone gene clusterRibosome biogenesisGene clusterHistone mRNATelomere maintenanceCellular functionsRNA speciesWidespread mechanismCell nucleiSurprising complexityBiochemical processesAltered affinityBody assemblyAssembly propertiesRibonucleoproteinDistinct structuresAssemblyPre-existing substructuresBiogenesisSplicingAdditional layerTranscription
2011
Cotranscriptional 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 ResearchMeSH KeywordsAnimalsChromatinHistonesHumansNucleosomesRNA Polymerase IIRNA SplicingTranscription, GeneticConceptsRNA polymerase II elongation rateContext of chromatinProtein-coding transcriptsRNA polymerase IIPre-mRNA splicingTranscript bodyTranscriptional pausingHistone modificationsPolymerase IIIntron removalSplicingTranscriptionElongation rateGenesTranscriptsRecent evidenceChromatinIntronsPausingElongationRegulatorLocal regulationRegulationRecruitmentThe In Vivo Kinetics of RNA Polymerase II Elongation during Co-Transcriptional Splicing
Brody Y, Neufeld N, Bieberstein N, Causse SZ, Böhnlein EM, Neugebauer KM, Darzacq X, Shav-Tal Y. The In Vivo Kinetics of RNA Polymerase II Elongation during Co-Transcriptional Splicing. PLOS Biology 2011, 9: e1000573. PMID: 21264352, PMCID: PMC3019111, DOI: 10.1371/journal.pbio.1000573.Peer-Reviewed Original ResearchMeSH KeywordsBeta-GlobinsFluorescence Recovery After PhotobleachingGreen Fluorescent ProteinsHumansIntronsInverted Repeat SequencesLac RepressorsRecombinant Fusion ProteinsRibonucleoproteins, Small NuclearRNA Polymerase IIRNA PrecursorsRNA SplicingRNA, MessengerSpliceosomesTranscription, GeneticTumor Cells, CulturedConceptsNumber of intronsU1 snRNPPol II elongation ratesRNA polymerase II elongationRNA polymerase II enzymeSplicing-independent roleTranscription elongation kineticsIntron-containing genesCo-transcriptional splicingPolymerase II elongationCompletion of splicingTranscribed pre-mRNARNA processing eventsInducible gene constructsPol II elongationElongation ratePolymerase elongation ratesNascent RNATranscriptional elongationIntronless genesSpliceosome componentsTranscription terminationSplicing machineryTranscription sitesGene end
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 simulationsIntronlessSpliceosomePausingYeastThe differential interaction of snRNPs with pre-mRNA reveals splicing kinetics in living cells
Huranová M, Ivani I, Benda A, Poser I, Brody Y, Hof M, Shav-Tal Y, Neugebauer KM, Staněk D. The differential interaction of snRNPs with pre-mRNA reveals splicing kinetics in living cells. Journal Of Cell Biology 2010, 191: 75-86. PMID: 20921136, PMCID: PMC2953428, DOI: 10.1083/jcb.201004030.Peer-Reviewed Original ResearchConceptsSmall nuclear RNP particlesPrecursor messenger RNA splicingMessenger RNA splicingBinding of U1Live-cell imagingRate of splicingNuclear RNP particlesLarge ribonucleoproteinSnRNP componentsRNA splicingSpliceosome assemblyAdditional proteinsRNP particlesHuman cellsSplicingLiving cellsCell nucleiDifferential interactionsEndogenous levelsSpliceosomeMRNARibonucleoproteinCell imagingCore componentCellsDynamic control of Cajal body number during zebrafish embryogenesis
Strzelecka M, Oates AC, Neugebauer KM. Dynamic control of Cajal body number during zebrafish embryogenesis. Nucleus 2010, 1: 96-108. PMID: 21327108, PMCID: PMC3035118, DOI: 10.4161/nucl.1.1.10680.Peer-Reviewed Original ResearchConceptsCajal bodiesEnd processing factorsGene expressionZygotic genome activationZygotic gene expressionRNA processing machineryDistinct nuclear bodiesMRNA splicing machineryCajal body numberLive-cell imagingCB numberHours of developmentGenome activationZebrafish embryogenesisNuclear subcompartmentsSnRNP biogenesisSplicing machineryZebrafish embryosCell divisionNuclear bodiesCB assemblyEmbryonic cellsMaternal contributionProcessing machineryEmbryos
2009
SR Protein Family Members Display Diverse Activities in the Formation of Nascent and Mature mRNPs In Vivo
Sapra AK, Änkö M, Grishina I, Lorenz M, Pabis M, Poser I, Rollins J, Weiland EM, Neugebauer KM. SR Protein Family Members Display Diverse Activities in the Formation of Nascent and Mature mRNPs In Vivo. Molecular Cell 2009, 34: 179-190. PMID: 19394295, DOI: 10.1016/j.molcel.2009.02.031.Peer-Reviewed Original ResearchMeSH KeywordsChromatin ImmunoprecipitationChromosomes, Artificial, BacterialFluorescence Resonance Energy TransferGenes, fosGreen Fluorescent ProteinsHeLa CellsHumansNuclear ProteinsPromoter Regions, GeneticRecombinant Fusion ProteinsRibonucleoproteinsRNA SplicingRNA-Binding ProteinsTranscription, GeneticConceptsRNA recognition motifSR proteinsCytoplasmic mRNAPol IIProtein interactionsSR protein family membersFRET/FLIMMRNA splicing factorsProtein family membersStable cell linesMRNP remodelingMRNA lifetimeGene regulationFormation of nascentSplicing factorsRecognition motifPromoter controlFamily membersAdditional roleProteinRNACell linesIndividual family membersMRNADiverse activities
1997
Transcription units as RNA processing units
Neugebauer K, Roth M. Transcription units as RNA processing units. Genes & Development 1997, 11: 3279-3285. PMID: 9407022, DOI: 10.1101/gad.11.24.3279.Peer-Reviewed Original ResearchDistribution 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