2024
Steering research on mRNA splicing in cancer towards clinical translation
Anczukow O, Allain F, Angarola B, Black D, Brooks A, Cheng C, Conesa A, Crosse E, Eyras E, Guccione E, Lu S, Neugebauer K, Sehgal P, Song X, Tothova Z, Valcárcel J, Weeks K, Yeo G, Thomas-Tikhonenko A. Steering research on mRNA splicing in cancer towards clinical translation. Nature Reviews Cancer 2024, 1-19. PMID: 39384951, DOI: 10.1038/s41568-024-00750-2.Peer-Reviewed Original ResearchSplicing aberrationsMRNA splicingLong-read RNA sequencingRNA sequencingShort-read RNA sequencingCopy number variationsMis-spliced transcriptsRecurrent somatic mutationsSynthetic lethal approachSingle-cell levelSpliceosome componentsSplicing alterationsSplicing factorsCellular processesNumber variationsSpliceosome inhibitorsMRNA isoformsDNA repairSplicingSomatic mutationsTumor vulnerabilitiesLethal approachHuman cancersCancer initiationCancer progressionEmerging 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
Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA
Draycott AS, Schaening-Burgos C, Rojas-Duran MF, Wilson L, Schärfen L, Neugebauer KM, Nachtergaele S, Gilbert WV. Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA. PLOS Biology 2022, 20: e3001622. PMID: 35609439, PMCID: PMC9129914, DOI: 10.1371/journal.pbio.3001622.Peer-Reviewed Original ResearchConceptsTranscriptome-wide mappingSmall nucleolar RNAsFunctional RNA structuresSingle-nucleotide resolutionStem-loop regionEukaryotic ribosomesNucleolar RNAsPre-mRNARNA structureRNA targetsDihydrouridine synthaseHuman diseasesMRNARNANovel classFunctional componentsSplicingTRNARibosomesYeastDependent changesLandscapeOrganismsDihydrouridineSequencing
2016
Splicing 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
2013
Counting on co-transcriptional splicing
Brugiolo M, Herzel L, Neugebauer KM. Counting on co-transcriptional splicing. Faculty Reviews 2013, 5: 9. PMID: 23638305, PMCID: PMC3619158, DOI: 10.12703/p5-9.Peer-Reviewed Original ResearchCo-transcriptional splicingMultiple model organismsProcess of transcriptionModel organismsSplicing machineryTranscription terminationSplicing eventsIntron removalMammalian cellsIntron sequencesBioinformatics analysisPlace coSplicingExperimental accessibilityMost cellsGlobal datasetTranscriptionOrganismsMRNAExperimental approachBroad differencesSpliceosomeInsectsCellsYeast
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 layerTranscriptionRNA–protein interactions in vivo: global gets specific
Änkö M, Neugebauer KM. RNA–protein interactions in vivo: global gets specific. Trends In Biochemical Sciences 2012, 37: 255-262. PMID: 22425269, DOI: 10.1016/j.tibs.2012.02.005.Peer-Reviewed Original ResearchConceptsNumerous protein domainsRNA-binding specificityRNA-protein interactionsEndogenous RNA moleculesShort RNA sequencesProperties of proteinsProtein domainsPolyadenylation factorsRNA moleculesRNA sequencesRNALimited repertoireProteinStructural determinationChaperonesCellsRecent advancesSplicingVivoSpecificitySequenceCrucial contributionDestabilizerRepertoireLocalization factorIntegration of Splicing with Nuclear and Cellular Events
Sapra A, Neugebauer K. Integration of Splicing with Nuclear and Cellular Events. 2012, 109-117. DOI: 10.1002/9783527636778.ch9.Peer-Reviewed Original Research
2011
Pause 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 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 componentCells
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