2024
Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms
Hong Y, Pasca S, Shi W, Puiu D, Lake N, Lek M, Ru M, Grove M, Prizment A, Joshu C, Platz E, Guallar E, Arking D, Gondek L. Mitochondrial heteroplasmy improves risk prediction for myeloid neoplasms. Nature Communications 2024, 15: 10133. PMID: 39578475, PMCID: PMC11584845, DOI: 10.1038/s41467-024-54443-3.Peer-Reviewed Original ResearchConceptsClonal hematopoiesis of indeterminate potentialClonal hematopoiesisVariant allele fractionHeteroplasmic variantsIndeterminate potentialMyeloid neoplasmsHeteroplasmyMultiple mutationsAllele fractionMutationsHigh-risk groupPathogenic risk factorsMarkersRisk score modelDeleteriousnessSpliceosomeHematologic malignanciesRisk stratificationNeoplasm developmentNeoplasmsNeoplasm incidenceRisk factorsVariants
2020
Visualizing group II intron dynamics between the first and second steps of splicing
Manigrasso J, Chillón I, Genna V, Vidossich P, Somarowthu S, Pyle AM, De Vivo M, Marcia M. Visualizing group II intron dynamics between the first and second steps of splicing. Nature Communications 2020, 11: 2837. PMID: 32503992, PMCID: PMC7275048, DOI: 10.1038/s41467-020-16741-4.Peer-Reviewed Original ResearchConceptsGroup II intron splicingGroup II intronsSelf-splicing ribozymesGene-editing toolsIntron dynamicsEukaryotic spliceosomeActive site dynamicsIntron splicingRetrotransposable elementsCatalytic triadSplicingMolecular machinesConformational changesFirst residueMultiple conformationsSite dynamicsSpliceosomeIntronsStructural rearrangementsX-ray crystallographyEnzymatic assayStructural dataEnzymatic strategyFunctional dataActive site
2018
Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA
Montemayor E, Didychuk A, Yake A, Sidhu G, Brow D, Butcher S. Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA. Nature Communications 2018, 9: 1749. PMID: 29717126, PMCID: PMC5931518, DOI: 10.1038/s41467-018-04145-4.Peer-Reviewed Original ResearchConceptsU6 small nuclear RNASmall nuclear RNAPre-mRNAU6 snRNPPre-mRNA substratePrecursor messenger RNAProtein-protein contactsC-terminal regionSaccharomyces cerevisiaeHeteroheptameric ringMature mRNAActive siteU6 snRNPsMRNA decayNuclear RNAPost-transcriptionallySpliceosomeLsm2Prp24SnRNPMessenger RNARNAMRNAIntronLSm8The life of U6 small nuclear RNA, from cradle to grave
Didychuk A, Butcher S, Brow D. The life of U6 small nuclear RNA, from cradle to grave. RNA 2018, 24: 437-460. PMID: 29367453, PMCID: PMC5855946, DOI: 10.1261/rna.065136.117.Peer-Reviewed Original ResearchConceptsU6 small nuclear RNASmall nuclear RNAPre-mRNANuclear RNAProcess of RNA splicingCatalyzes intron removalEukaryotic gene expressionPre-mRNA substrateUridine-rich small nuclear RNAsRemoval of intronsPrecursor messenger RNACryo-EM structureSplicing cycleNoncoding transcriptsCatalytic coreProtein partnersRNA splicingIntron removalSplice siteGenetic dataMacromolecular machinesSpliceosomeGene expressionSplicingConformational changes
2017
Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities
Didychuk A, Montemayor E, Carrocci T, DeLaitsch A, Lucarelli S, Westler W, Brow D, Hoskins A, Butcher S. Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities. Nature Communications 2017, 8: 497. PMID: 28887445, PMCID: PMC5591277, DOI: 10.1038/s41467-017-00484-w.Peer-Reviewed Original ResearchMeSH KeywordsCatalytic DomainCrystallography, X-RayEvolution, MolecularGenetic VariationHumansModels, MolecularPhosphoric Diester HydrolasesProtein BindingProtein DomainsRibonucleoprotein, U4-U6 Small NuclearRNA, Small NuclearSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSubstrate SpecificityConceptsU6 snRNP assemblySmall nuclear ribonucleoproteinSnRNP assemblyCognate RNA-binding proteinsTerminal 3'-phosphateU6 small nuclear ribonucleoproteinsRNA-binding proteinsAnti-cooperative interactionsCyclic phosphodiesterase activitySpliceosome assemblyU6 RNAHuman orthologNuclear ribonucleoproteinUSB1SpliceosomeYeastProteinPhosphodiesterase activityAntagonist proteinComplex seriesAssemblyPrp24LHP1OrthologsSnRNAStructure and conformational plasticity of the U6 small nuclear ribonucleoprotein core
Montemayor E, Didychuk A, Liao H, Hu P, Brow D, Butcher S. Structure and conformational plasticity of the U6 small nuclear ribonucleoprotein core. Acta Crystallographica Section D, Structural Biology 2017, 73: 1-8. PMID: 28045380, PMCID: PMC5331471, DOI: 10.1107/s2059798316018222.Peer-Reviewed Original ResearchInternal stem-loopRNA recognition motifSmall nuclear ribonucleoproteinU6 internal stem-loopSplicing of precursor messenger RNAU6 small nuclear RNAProtein-RNA interfacesU6 small nuclear ribonucleoproteinsPrecursor messenger RNASmall nuclear RNAGel shift assaysStem-loopRibonucleoprotein complexCrystal structureGenetic dataNuclear ribonucleoproteinNuclear RNAConformational plasticityWild-typePrp24RNASpliceosomeElectrophoretic mobilityMessenger RNARibonucleoprotein
2016
A multi-step model for facilitated unwinding of the yeast U4/U6 RNA duplex
Rodgers M, Didychuk A, Butcher S, Brow D, Hoskins A. A multi-step model for facilitated unwinding of the yeast U4/U6 RNA duplex. Nucleic Acids Research 2016, 44: 10912-10928. PMID: 27484481, PMCID: PMC5159527, DOI: 10.1093/nar/gkw686.Peer-Reviewed Original ResearchConceptsSmall nuclear RNATri-snRNPU4/U6 unwindingU6 small nuclear RNAImpairs yeast growthSpliceosome active siteU4/U6 di-snRNPSmall nuclear ribonucleoproteinTri-snRNP assemblySpliceosome formationStrand invasionDi-snRNPYeast growthNuclear ribonucleoproteinNuclear RNARNA complexResonance energy transferSpliceosomeRNA duplexesForster resonance energy transferConformational rearrangementsDNA oligonucleotidesStem IIUnwindingU4/U6Splicing 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. F1000Research 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
Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing
Nag A, Steitz JA. Tri-snRNP-associated proteins interact with subunits of the TRAMP and nuclear exosome complexes, linking RNA decay and pre-mRNA splicing. RNA Biology 2012, 9: 334-342. PMID: 22336707, PMCID: PMC3384585, DOI: 10.4161/rna.19431.Peer-Reviewed Original ResearchConceptsDecay machineryMRNA splicingRNA decay machineryRNA decay factorsTri-snRNP complexNuclear exosome complexPM/SclYeast counterpartIntergenic transcriptsSnoRNA biogenesisExosome complexTri-snRNPRNA decayRRNA processingPhosphorylation sitesMRNA processingPutative componentsMtr4Prp31MachinerySplicingDifferent pathwaysProteinSpliceosomeBiogenesis
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
2009
Tertiary architecture of the Oceanobacillus iheyensis group II intron
Toor N, Keating KS, Fedorova O, Rajashankar K, Wang J, Pyle AM. Tertiary architecture of the Oceanobacillus iheyensis group II intron. RNA 2009, 16: 57-69. PMID: 19952115, PMCID: PMC2802037, DOI: 10.1261/rna.1844010.Peer-Reviewed Original ResearchConceptsGroup II intronsPotential evolutionary relationshipsGroup II intron structureGroup IIC intronIntron structureEvolutionary relationshipsEukaryotic spliceosomeInteraction networksRNA moleculesIntronsTertiary structural organizationGenetic studiesRibose zipperRNA foldingTertiary interactionsLarge ribozymesInteraction nodesStructural organizationTertiary architectureEukaryotesSpliceosomeGene therapyGenomeZipperFoldingDrosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron
Borah S, Wong AC, Steitz JA. Drosophila hnRNP A1 homologs Hrp36/Hrp38 enhance U2-type versus U12-type splicing to regulate alternative splicing of the prospero twintron. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 2577-2582. PMID: 19196985, PMCID: PMC2636732, DOI: 10.1073/pnas.0812826106.Peer-Reviewed Original ResearchConceptsU12-type splicingPurine-rich elementAlternative splicingMRNA undergoes alternative splicingTranscription factor ProsperoU12-type spliceosomeHeterogeneous nuclear ribonucleoprotein A1Undergoes alternative splicingU2-type spliceosomeDrosophila homologDrosophila embryogenesisS2 cellsHnRNP A1TwintronSplicingNeuronal differentiationHrp38SpliceosomeIntronsEmbryogenesisProteinAxonal outgrowthHrp36HnRNPsHomolog
2008
Minor-class splicing occurs in the nucleus of the Xenopus oocyte
Friend K, Kolev NG, Shu MD, Steitz JA. Minor-class splicing occurs in the nucleus of the Xenopus oocyte. RNA 2008, 14: 1459-1462. PMID: 18567814, PMCID: PMC2491479, DOI: 10.1261/rna.1119708.Peer-Reviewed Original ResearchConceptsSmall nuclear ribonucleoproteinMinor class intronsU12-type splicingXenopus oocytesU12-dependent intronsNuclear envelope breakdownCertain eukaryotesMinor spliceosomeVertebrate cellsSplicing substrateNuclear compartmentNuclear ribonucleoproteinRNA intronsAccurate splicingEnvelope breakdownSplicingIntronsCytoplasmOocytesEukaryotesSpliceosomeMeiosisRibonucleoproteinNucleusSmall fraction
2004
Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay
Hirose T, Shu MD, Steitz JA. Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 17976-17981. PMID: 15608055, PMCID: PMC539812, DOI: 10.1073/pnas.0408435102.Peer-Reviewed Original ResearchMeSH KeywordsCell LineCell NucleusCodon, NonsenseDNA, ComplementaryEvolution, MolecularExonsGene Expression RegulationHeLa CellsHumansImmunoprecipitationIntronsMutagenesis, Site-DirectedOpen Reading FramesPlasmidsRibonuclease HRibonucleoproteins, Small NuclearRNARNA PrecursorsRNA SplicingRNA, MessengerRNA, Small NuclearSpliceosomesTime FactorsTransfectionConceptsExon junction complexU12-type intronsOpen reading frameNonsense-mediated mRNA decayU12-type spliceosomeNonsense-mediated decaySmall nuclear ribonucleoproteinU2-type spliceosomePremature termination codonEJC assemblyMetazoan cellsMRNA decayEvolutionary ageDownstream functionsIntron removalNuclear ribonucleoproteinReading frameExon junctionsTermination codonJunction complexGene expressionIntron downstreamSpliceosomeIntronsSplicingAn Intronic Enhancer Regulates Splicing of the Twintron of Drosophila melanogaster prospero Pre-mRNA by Two Different Spliceosomes
Scamborova P, Wong A, Steitz JA. An Intronic Enhancer Regulates Splicing of the Twintron of Drosophila melanogaster prospero Pre-mRNA by Two Different Spliceosomes. Molecular And Cellular Biology 2004, 24: 1855-1869. PMID: 14966268, PMCID: PMC350559, DOI: 10.1128/mcb.24.5.1855-1869.2004.Peer-Reviewed Original ResearchConceptsPurine-rich elementSplicing pathwaySplice siteU12-type spliceosomeU12-type splicingVitro splicing systemForms of mRNAAlternative splicingEarly embryogenesisKc cellsIntron sequencesPre-mRNASystematic deletionIntronic enhancerSplicingSequence requirementsIntron regionsEnhancer elementsNucleotides downstreamMolecular mechanismsTwintronSpliceosomeSplicing systemMutation analysisPathway
2002
The splicing of U12‐type introns can be a rate‐limiting step in gene expression
Patel AA, McCarthy M, Steitz JA. The splicing of U12‐type introns can be a rate‐limiting step in gene expression. The EMBO Journal 2002, 21: 3804-3815. PMID: 12110592, PMCID: PMC126102, DOI: 10.1093/emboj/cdf297.Peer-Reviewed Original ResearchConceptsU12-type intronsGene expressionDrosophila melanogaster S2 cellsProtein-coding genesU12-type spliceosomePost-transcriptional regulationHuman tissue culture cellsU2-type intronsMetazoan genomesTissue culture cellsS2 cellsU12-typeIntron removalIdentical mRNAIntronsFluorescent proteinQuantitative RT-PCR assayMinigene constructsCulture cellsRate-limiting stepSpliceosomeMRNAMinor classExpressionRT-PCR assaysThe Divergent U12-Type Spliceosome Is Required for Pre-mRNA Splicing and Is Essential for Development in Drosophila
Otake LR, Scamborova P, Hashimoto C, Steitz JA. The Divergent U12-Type Spliceosome Is Required for Pre-mRNA Splicing and Is Essential for Development in Drosophila. Molecular Cell 2002, 9: 439-446. PMID: 11864616, DOI: 10.1016/s1097-2765(02)00441-0.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsAnimals, Genetically ModifiedBase SequenceDrosophila melanogasterDrosophila ProteinsGenes, LethalIntronsLarvaMolecular Sequence DataMutagenesis, InsertionalNerve Tissue ProteinsNuclear ProteinsNucleic Acid ConformationProtein IsoformsRibonucleoprotein, U4-U6 Small NuclearRibonucleoproteins, Small NuclearRNA PrecursorsRNA SplicingRNA, Small NuclearSequence AlignmentSequence Homology, Nucleic AcidSpliceosomesTranscription FactorsTransgenesConceptsU12-type spliceosomeThird instar larvalU12-type intronsPre-mRNA splicingU4atac/U6atacMetazoan organismsHomeodomain proteinsU5 snRNPsDrosophila melanogasterU12 spliceosomeMRNA intronsU12 snRNASingle locusU6atacInstar larvalSpliceosomeEmbryonic stagesCNS developmentIntronsMinor classU12DrosophilaMelanogasterVertebratesSnRNPs
1997
Developmental expression of the murine spliceosome‐associated protein mSAP49
Ruiz‐Lozano P, Doevendans P, Brown A, Gruber P, Chien K. Developmental expression of the murine spliceosome‐associated protein mSAP49. Developmental Dynamics 1997, 208: 482-490. PMID: 9097020, DOI: 10.1002/(sici)1097-0177(199704)208:4<482::aid-aja4>3.0.co;2-e.Peer-Reviewed Original ResearchConceptsRNA recognition motifTissue-specific splicingBasic C-terminusAmino acid sequencePeak of expressionHuman spliceosomeSpliceosome componentsSitu hybridization analysisMouse homologueRecognition motifRNA stabilizationAcid sequenceCardiac developmentC-terminusMouse embryosN-terminusNorthern analysisEmbryonic tissuesDevelopmental expressionHybridization analysisDay 11.5Optic vesicleMRNA distributionDay 13.5Spliceosome
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