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 RNAMultiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy
Podszywalow-Bartnicka P, Neugebauer K. Multiple roles for AU-rich RNA binding proteins in the development of haematologic malignancies and their resistance to chemotherapy. RNA Biology 2024, 21: 1-17. PMID: 38798162, PMCID: PMC11135835, DOI: 10.1080/15476286.2024.2346688.Peer-Reviewed Original ResearchConceptsARE-binding proteinsRNA-binding proteinsAU-rich elementsStress granulesBinding proteinTranslational regulation of mRNAsImpact alternative splicingCytoplasmic stress granulesProtein-RNA bindingAdaptation to microenvironmentProtein-RNA networksBinding to AU-rich elementsCancer cell proteomePost-transcriptional regulationAU-rich RNA-binding proteinsRegulation of mRNAsChemotherapy resistanceGene expression levelsSequence motifsProtein-RNAMRNA structureMature mRNATranslational regulationAlternative splicingCell proteome
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 changesLandscapeOrganismsDihydrouridineSequencingPrecision 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
2021
Generation of scalable cancer models by combining AAV-intron-trap, CRISPR/Cas9, and inducible Cre-recombinase
Boddu PC, Gupta AK, Kim JS, Neugebauer KM, Waldman T, Pillai MM. Generation of scalable cancer models by combining AAV-intron-trap, CRISPR/Cas9, and inducible Cre-recombinase. Communications Biology 2021, 4: 1184. PMID: 34645977, PMCID: PMC8514589, DOI: 10.1038/s42003-021-02690-1.Peer-Reviewed Original ResearchDMA-tudor interaction modules control the specificity of in vivo condensates
Courchaine EM, Barentine AES, Straube K, Lee DR, Bewersdorf J, Neugebauer KM. DMA-tudor interaction modules control the specificity of in vivo condensates. Cell 2021, 184: 3612-3625.e17. PMID: 34115980, PMCID: PMC8402948, DOI: 10.1016/j.cell.2021.05.008.Peer-Reviewed Original ResearchMaternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activation
2020
Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Fauver JR, Petrone ME, Hodcroft EB, Shioda K, Ehrlich HY, Watts AG, Vogels CBF, Brito AF, Alpert T, Muyombwe A, Razeq J, Downing R, Cheemarla NR, Wyllie AL, Kalinich CC, Ott IM, Quick J, Loman NJ, Neugebauer KM, Greninger AL, Jerome KR, Roychoudhury P, Xie H, Shrestha L, Huang ML, Pitzer VE, Iwasaki A, Omer SB, Khan K, Bogoch II, Martinello RA, Foxman EF, Landry ML, Neher RA, Ko AI, Grubaugh ND. Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States. Cell 2020, 181: 990-996.e5. PMID: 32386545, PMCID: PMC7204677, DOI: 10.1016/j.cell.2020.04.021.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Federal travel restrictionsSARS-CoV-2 transmissionCOVID-19 patientsCoronavirus SARS-CoV-2SARS-CoV-2 introductionsEarly SARS-CoV-2 transmissionPattern of spreadSustained transmissionLocal surveillanceEarly epidemicInternational importationCOVID-19 outbreakUnited StatesViral genomeInternational travel patternsPatientsCritical needTravel restrictions
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
RNA tales – how embryos read and discard messages from mom
Despic V, Neugebauer KM. RNA tales – how embryos read and discard messages from mom. Journal Of Cell Science 2018, 131: jcs201996. PMID: 29467249, DOI: 10.1242/jcs.201996.Peer-Reviewed Original ResearchConceptsZygotic genomePost-transcriptional regulatory pathwaysMaternal mRNA clearanceMaternal mRNA degradationEarly developmentContribution of microRNAsZygotic transitionMRNA clearanceRNA regulationMRNA decayCellular contextHigh-throughput methodZebrafish embryosFemale gametesMaternal mRNAsMolecular playersMRNA degradationRNA modificationsMolecular principlesRegulatory pathwaysGenomeLater stepsMZTSilent genomeEmbryosDynamics 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
2017
Cellular differentiation state modulates the mRNA export activity of SR proteins
Botti V, McNicoll F, Steiner MC, Richter FM, Solovyeva A, Wegener M, Schwich OD, Poser I, Zarnack K, Wittig I, Neugebauer KM, Müller-McNicoll M. Cellular differentiation state modulates the mRNA export activity of SR proteins. Journal Of Cell Biology 2017, 216: 1993-2009. PMID: 28592444, PMCID: PMC5496613, DOI: 10.1083/jcb.201610051.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsArginineCell DifferentiationCell NucleusDNA-Binding ProteinsHeLa CellsHumansImmunoprecipitationMethylationMiceNeurogenesisPhenotypePhosphorylationPluripotent Stem CellsProtein BindingProtein Processing, Post-TranslationalRepressor ProteinsRNA InterferenceRNA, MessengerRNA-Binding ProteinsSerine-Arginine Splicing FactorsTandem Mass SpectrometryTranscription FactorsTransfectionConceptsMRNA export activitySR proteinsP19 cellsMRNA exportSR protein family membersProtein-RNA interactionsMurine P19 cellsCellular differentiation stateProtein family membersLower phosphorylation levelsArginine methylationPluripotency factorsCytoplasmic mRNA levelsMRNA processingPosttranslational modificationsCellular dynamicsDifferentiated cellsNeural differentiationSRSF5Differentiation statePhosphorylation levelsHeLa cellsProteinExport activityMRNA levelsSpecial focus on the Cajal Body
Neugebauer KM. Special focus on the Cajal Body. RNA Biology 2017, 14: 669-670. PMID: 28486008, PMCID: PMC5519238, DOI: 10.1080/15476286.2017.1316928.Peer-Reviewed Original Research
2015
Coilin: The first 25 years
Machyna M, Neugebauer KM, Staněk D. Coilin: The first 25 years. RNA Biology 2015, 12: 590-596. PMID: 25970135, PMCID: PMC4615369, DOI: 10.1080/15476286.2015.1034923.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 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 mechanismTranscriptsThe Coilin Interactome Identifies Hundreds of Small Noncoding RNAs that Traffic through Cajal Bodies
Machyna M, Kehr S, Straube K, Kappei D, Buchholz F, Butter F, Ule J, Hertel J, Stadler PF, Neugebauer KM. The Coilin Interactome Identifies Hundreds of Small Noncoding RNAs that Traffic through Cajal Bodies. Molecular Cell 2014, 56: 389-399. PMID: 25514182, DOI: 10.1016/j.molcel.2014.10.004.Peer-Reviewed Original ResearchConceptsCajal bodiesSmall nucleolar RNAsSmall nuclear RNASmall noncoding RNAsChIP-seq peaksCoilin proteinSnoRNA biogenesisRNP assemblySnRNP assemblyNcRNA metabolismSnRNA genesSubnuclear compartmentsCellular hubHuman snoRNAsMolecular functionsSnRNA transcriptsNucleolar RNAsNoncoding RNAsNuclear RNACoilinRNASignal trafficRole of CBAssemblySnRNAs
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 layerTranscriptionFirst 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 lengthRNA–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 factor