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 progression
2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kineticsTranscription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape
Boddu P, Gupta A, Roy R, Herrero A, Verma A, Neugebauer K, Pillai M. Transcription Defects in SF3B1K700E Induce Targetable Alterations in the Chromatin Landscape. Blood 2023, 142: 709. DOI: 10.1182/blood-2023-188083.Peer-Reviewed Original ResearchChromatin organizationSuch epigenetic changesGenome editing approachesRNA splicing factorsChromatin landscapeSingle mutant alleleEpigenetic landscapeGenomic integrityTranscription defectTranscription kineticsSplicing factorsChIP-seqEpigenetic regulatorsEpigenetic changesEpigenetic therapyMutant allelesEditing approachesFactor mutationsK562 cell lineDownstream effectsCell linesMyeloid disordersClonal myeloid disordersHDAC pathwayMutations
2017
Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition
Despic V, Dejung M, Gu M, Krishnan J, Zhang J, Herzel L, Straube K, Gerstein MB, Butter F, Neugebauer KM. Dynamic RNA–protein interactions underlie the zebrafish maternal-to-zygotic transition. Genome Research 2017, 27: 1184-1194. PMID: 28381614, PMCID: PMC5495070, DOI: 10.1101/gr.215954.116.Peer-Reviewed Original ResearchConceptsZygotic genome activationRNA-protein interactionsMaternal mRNAsZygotic transitionSplicing factorsDynamic RNA-protein interactionsMRNA interactome capturePost-transcriptional regulationMRNA splicing factorsRNA processing eventsTranscription-dependent mannerNumerous splicing factorsInteractome captureGenome activationSequence-specific associationHnRNP proteinsRNA metabolismDramatic translocationZebrafish embryosProcessing eventsICLIP dataDevelopmental transitionsRNA targetsReporter assaysProtein constellations
2012
Integration 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 ResearchSplicing 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 purification
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
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