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 RNATranscription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant state
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
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 ResearchConceptsShort 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
2012
First Exon Length Controls Active Chromatin Signatures and Transcription
Bieberstein NI, Oesterreich F, Straube K, Neugebauer KM. First Exon Length Controls Active Chromatin Signatures and Transcription. Cell Reports 2012, 2: 62-68. PMID: 22840397, DOI: 10.1016/j.celrep.2012.05.019.Peer-Reviewed Original ResearchConceptsGeneral transcription factorsTranscription start siteFirst exonShort first exonExon-intron organizationGenome-wide analysisHistone modifications H3K4me3Active chromatin signatureRNA polymerase IIRole of splicingTransgenic cell linesChIP-seq dataLong first exonChromatin signaturesGene architectureExon-intron boundariesHigh expression levelsAntisense transcriptionTranscriptional outputPolymerase IIH3K4me3 levelsGene activityTSS usageTranscription factorsExon lengthSplicing Factor ChIP and ChRIP: Detection of Splicing and Splicing Factors at Genes by Chromatin Immunoprecipitation
Sapra A, Oesterreich F, Pabis M, Listerman I, Bardehle N, Neugebauer K. Splicing Factor ChIP and ChRIP: Detection of Splicing and Splicing Factors at Genes by Chromatin Immunoprecipitation. 2012, 416-427. DOI: 10.1002/9783527636778.ch39.Peer-Reviewed Original ResearchNascent RNASplicing factorsChromatin immunoprecipitationRNA processing intermediatesMammalian tissue culture cellsRNA processing factorsRNA polymerase IIRNA processing eventsGene of interestTissue culture cellsPolymerase IIActive histoneMRNA processingIsolation of RNAProcessing factorsProcessing eventsRNA immunoprecipitationChromatinNucleic acid complexesQuantitative RT-PCRLiving cellsProcessing intermediatesRNACulture cellsImmunoprecipitation
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 ResearchConceptsRNA polymerase II elongation rateContext of chromatinProtein-coding transcriptsRNA polymerase IIPre-mRNA splicingTranscript bodyTranscriptional pausingHistone modificationsPolymerase IIIntron removalSplicingTranscriptionElongation rateGenesTranscriptsRecent evidenceChromatinIntronsPausingElongationRegulatorLocal regulationRegulationRecruitment