2022
DNA processing by the Kaposi's sarcoma-associated herpesvirus alkaline exonuclease SOX contributes to viral gene expression and infectious virion production
Hartenian E, Mendez A, Didychuk A, Khosla S, Glaunsinger B. DNA processing by the Kaposi's sarcoma-associated herpesvirus alkaline exonuclease SOX contributes to viral gene expression and infectious virion production. Nucleic Acids Research 2022, 51: 182-197. PMID: 36537232, PMCID: PMC9841436, DOI: 10.1093/nar/gkac1190.Peer-Reviewed Original ResearchConceptsKaposi's sarcoma-associated herpesvirusAlkaline exonucleaseInfectious virion productionViral gene expressionDNA processingStructure-guided functional analysesGene expressionDNA substrate preferenceVirion productionKingdoms of lifeCleavage of mRNAGammaherpesvirus Kaposi's sarcoma-associated herpesvirusViral DNA processingLifecycles of virusesBacteriophage LSoxS mutantFunctional conservationGenome replicationGenetic conservationSarcoma-associated herpesvirusPhage LSubstrate preferenceDNA bindingHuman gammaherpesviruses Kaposi's sarcoma-associated herpesvirusSOX activityBetter late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses
Dremel S, Didychuk A. Better late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses. Seminars In Cell And Developmental Biology 2022, 146: 57-69. PMID: 36535877, PMCID: PMC10101908, DOI: 10.1016/j.semcdb.2022.12.001.Peer-Reviewed Original ResearchConceptsViral transcriptional activityViral preinitiation complexPol IITranscription of late genesGene transcriptionCellular RNA polymerase IITATA-binding proteinRNA polymerase IIModified TATA boxCis-acting elementsSubfamily of herpesvirusesPolymerase IITATA boxPreinitiation complexConsensus sequenceLate genesTranscriptional activityGene promoterLytic replicationGenesTemporal cascadeTranscriptionViral mimicPolPromoterThe transition phase: preparing to launch a laboratory
McKinley K, Didychuk A, Nicholas D, Termini C. The transition phase: preparing to launch a laboratory. Trends In Biochemical Sciences 2022, 47: 814-818. PMID: 35644775, PMCID: PMC9677455, DOI: 10.1016/j.tibs.2022.05.002.Peer-Reviewed Original ResearchA Two-tiered functional screen identifies herpesviral transcriptional modifiers and their essential domains
Morgens D, Nandakumar D, Didychuk A, Yang K, Glaunsinger B. A Two-tiered functional screen identifies herpesviral transcriptional modifiers and their essential domains. PLOS Pathogens 2022, 18: e1010236. PMID: 35041709, PMCID: PMC8797222, DOI: 10.1371/journal.ppat.1010236.Peer-Reviewed Original ResearchConceptsViral DNA replicationKaposi's sarcoma-associated herpesvirusViral genomeDsDNA virusesLate genesDNA replicationTranscriptional activityViral sequencesViral transcriptional activityCatalytic domainIndividual mutantsSgRNA librarySarcoma-associated herpesvirusTiling screensDNA bindingDeep sequencingBase pairsFunctional screeningCut sitePooled screeningTranscriptional modifiersDNA virusesGenomeEssential domainsGene expression
2021
A pentameric protein ring with novel architecture is required for herpesviral packaging
Didychuk A, Gates S, Gardner M, Strong L, Martin A, Glaunsinger B. A pentameric protein ring with novel architecture is required for herpesviral packaging. ELife 2021, 10: e62261. PMID: 33554858, PMCID: PMC7889075, DOI: 10.7554/elife.62261.Peer-Reviewed Original ResearchConceptsViral genomeAccessory factorsBind double-stranded DNAPositively charged central channelContext of KSHV infectionDouble-stranded DNA virusesPositively charged residuesOncogenic herpesvirus Kaposi's sarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirusDouble-stranded DNASarcoma-associated herpesvirusGenome packagingHomologous proteinsNascent capsidsDNA bindingProtein ringGenomePackaging motorDNA virusesCharged residuesProgeny virionsMolecular motorsCentral channelKSHV infectionMutants
2020
The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription
Castañeda A, Didychuk A, Louder R, McCollum C, Davis Z, Nogales E, Glaunsinger B. The gammaherpesviral TATA-box-binding protein directly interacts with the CTD of host RNA Pol II to direct late gene transcription. PLOS Pathogens 2020, 16: e1008843. PMID: 32886723, PMCID: PMC7498053, DOI: 10.1371/journal.ppat.1008843.Peer-Reviewed Original ResearchConceptsTATA box-binding proteinRNA polymerase IIN-terminal domainPol IIPolymerase IICellular TATA box binding proteinHost RNA polymerase IIRecruitment of RNA polymerase IIGene transcriptionLate gene transcriptionPol II recruitmentProtein interaction studiesProtein-protein contactsC-terminal domainEukaryotic transcriptionPolymerase recruitmentHuman cytomegalovirusPreinitiation complexHost transcriptionRNA PolLate genesMicroscopy-based imagingKaposi's sarcoma-associated virusTranscriptional activityPromoter recognitionConserved CxnC Motifs in Kaposi’s Sarcoma-Associated Herpesvirus ORF66 Are Required for Viral Late Gene Expression and Are Essential for Its Interaction with ORF34
Didychuk A, Castañeda A, Kushnir L, Huang C, Glaunsinger B. Conserved CxnC Motifs in Kaposi’s Sarcoma-Associated Herpesvirus ORF66 Are Required for Viral Late Gene Expression and Are Essential for Its Interaction with ORF34. Journal Of Virology 2020, 94: 10.1128/jvi.01299-19. PMID: 31578296, PMCID: PMC6955276, DOI: 10.1128/jvi.01299-19.Peer-Reviewed Original ResearchConceptsViral preinitiation complexKaposi's sarcoma-associated herpesvirusC-terminal domainCysteine-rich motifHost transcription machineryPreinitiation complexGene promoterTranscription machinerySarcoma-associated herpesvirusLate genesGene transcriptionViral late gene expressionZinc finger motifsLate gene transcriptionSequence-specific bindingTranscriptional regulatory activityLate gene expressionLate gene promotersInfectious virionsProduction of capsid proteinsRelease of infectious virionsViral replication cycleFinger motifPromoter occupancySequence-specific
2018
The 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 seriesAssemblyPrp24LHP1OrthologsSnRNA