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, 24: 887-905. 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 kinetics
2014
Nuclear bodies: RNA‐rich powerhouses of the cell (471.3)
Neugebauer K, Machyna M, Straube K, Heyn P. Nuclear bodies: RNA‐rich powerhouses of the cell (471.3). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.471.3.Peer-Reviewed Original ResearchHistone locus bodyCajal bodiesNuclear bodiesZygotic genome activationTrafficking of RNAsEarly zebrafish embryogenesisSites of transcriptionSite of assemblyGenome activationSpliceosomal snRNPsZebrafish embryogenesisRNA processingHistone mRNAMRNA splicingEnd formationMacromolecular complexesLow-affinity interactionsNuclear morphologyCell nucleiCommon organizational featuresLipid bilayersRNAEfficient assemblyDifferent functionsMolecular composition
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