2021
SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes
Pawlica P, Yario TA, White S, Wang J, Moss WN, Hui P, Vinetz JM, Steitz JA. SARS-CoV-2 expresses a microRNA-like small RNA able to selectively repress host genes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2116668118. PMID: 34903581, PMCID: PMC8719879, DOI: 10.1073/pnas.2116668118.Peer-Reviewed Original ResearchConceptsBasic leucine zipper ATF-like transcription factor 2Small RNAsHuman lung-derived cell linesSARS-CoV-2 infectionLung-derived cell linesRNA interference (RNAi) pathwayHost miRNA levelsTranscription factor 2Cellular machineryInterference pathwayDrosha proteinSARS-CoV-2-infected individualsHost genesSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Host miRNAsPutative targetsSyndrome coronavirus 2SARS-CoV-2MiRNA levelsFactor 2Cell linesNasopharyngeal swabsCoronavirus 2
2019
Idiosyncrasies of Viral Noncoding RNAs Provide Insights into Host Cell Biology
Withers JB, Mondol V, Pawlica P, Rosa-Mercado NA, Tycowski KT, Ghasempur S, Torabi SF, Steitz JA. Idiosyncrasies of Viral Noncoding RNAs Provide Insights into Host Cell Biology. Annual Review Of Virology 2019, 6: 1-21. PMID: 31039329, PMCID: PMC6768742, DOI: 10.1146/annurev-virology-092818-015811.Peer-Reviewed Original ResearchConceptsHost cell biologyCell biologyMessenger RNA stabilityHost cell machineryHost gene expressionDiverse biological rolesHost immune evasionLong ncRNAsMicroRNA biogenesisCell machineryNoncoding RNAsRNA stabilityCircular RNAsCellular transformationCellular survivalNcRNAsViral noncoding RNAsBiological roleGene expressionAnimal virusesNoncanonical pathwayHost cellsViral ncRNAsNovel mechanismBiogenesis
2018
Two herpesviral noncoding PAN RNAs are functionally homologous but do not associate with common chromatin loci
Withers JB, Li ES, Vallery TK, Yario TA, Steitz JA. Two herpesviral noncoding PAN RNAs are functionally homologous but do not associate with common chromatin loci. PLOS Pathogens 2018, 14: e1007389. PMID: 30383841, PMCID: PMC6233925, DOI: 10.1371/journal.ppat.1007389.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell NucleusChromatinGene Expression Regulation, ViralGene Knockdown TechniquesHEK293 CellsHerpesviridaeHerpesviridae InfectionsHerpesvirus 8, HumanHost-Pathogen InteractionsHumansMacaca mulattaRhadinovirusRNA, Long NoncodingRNA, MessengerRNA, NuclearRNA, ViralTumor Virus InfectionsViral ProteinsVirus ReplicationConceptsKaposi's sarcoma-associated herpesvirusPAN RNAPAN RNA expressionGene expressionChromatin lociSarcoma-associated herpesvirusViral mRNAsSpecific chromatin lociNuclear mRNA exportNucleotide sequence conservationAbundant nuclear RNARNA expressionLytic viral gene expressionViral gene expressionMRNA exportRNA associationSequence conservationPolyadenylated transcriptsViral chromatinLoci differHost chromatinRNA functionCell fractionationNuclear RNAProgeny virion releaseKaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear RNA
Vallery TK, Withers JB, Andoh JA, Steitz JA. Kaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear RNA. Journal Of Virology 2018, 92: 10.1128/jvi.00220-18. PMID: 29643239, PMCID: PMC6002709, DOI: 10.1128/jvi.00220-18.Peer-Reviewed Original ResearchConceptsKaposi's sarcoma-associated herpesvirusViral replication compartmentsSarcoma-associated herpesvirusReplication compartmentsViral DNA replicationViral DNA synthesisPAN RNANuclear fociDNA replicationNuclear RNAViral mRNAsDNA synthesisViral transcriptsLytic phaseIntronless viral mRNAsHijack host machineryActive viral DNA replicationPolyadenylated Nuclear RNAHost cell nucleusViral noncoding RNAViral RNA accumulationShutoff effectHuman cell hostSpatiotemporal regulationViral life cycle
2016
Myriad Triple-Helix-Forming Structures in the Transposable Element RNAs of Plants and Fungi
Tycowski KT, Shu MD, Steitz JA. Myriad Triple-Helix-Forming Structures in the Transposable Element RNAs of Plants and Fungi. Cell Reports 2016, 15: 1266-1276. PMID: 27134163, PMCID: PMC4864102, DOI: 10.1016/j.celrep.2016.04.010.Peer-Reviewed Original ResearchConceptsTransposable elementsCellular noncoding RNAsPotential evolutionary consequencesCis-acting RNA structuresIntron lossEvolutionary consequencesBioinformatic identificationTE transcriptsReporter transcriptFish speciesNoncoding RNAsElement RNAHorizontal transferRNA structureTransposase geneRich tractHuman cellsTriple helix formationBase triplesRNAEne coreTranscriptsTriple helixIntronlessGenomeEBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression
Lee N, Yario TA, Gao JS, Steitz JA. EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 3221-3226. PMID: 26951683, PMCID: PMC4812724, DOI: 10.1073/pnas.1601773113.Peer-Reviewed Original ResearchConceptsNon-POU domain-containing octamer-binding proteinGene expressionNoncoding RNAsHost RNAAbundant noncoding RNAsCellular noncoding RNAsRNA-protein crosslinkingOctamer-binding proteinHost gene expressionBox protein 5Viral gene expressionHost transcription factorsGlutamine richFactor prolineIntermediary proteinsNuclear bodiesTranscription factorsRNA 2Host proteinsRecombinant proteinsProtein resultsProtein componentsProtein 5Protein 14RNA
2015
Proteomics and Transcriptomics of BJAB Cells Expressing the Epstein-Barr Virus Noncoding RNAs EBER1 and EBER2
Pimienta G, Fok V, Haslip M, Nagy M, Takyar S, Steitz JA. Proteomics and Transcriptomics of BJAB Cells Expressing the Epstein-Barr Virus Noncoding RNAs EBER1 and EBER2. PLOS ONE 2015, 10: e0124638. PMID: 26121143, PMCID: PMC4487896, DOI: 10.1371/journal.pone.0124638.Peer-Reviewed Original ResearchConceptsMRNA-seq dataHost cell nucleusBJAB cellsCell proliferationGene expression featuresPro-survival effectsProtein adaptersAlternative splicingMRNA transcriptomeUpregulated proteinsSILAC dataRich elementsAkt activationPI3K-AktBiochemical assaysCell nucleiEBV latencySwitch eventsProteinMaintenance of latencyCell linesVEGFA proteinMechanistic explanationUpregulated oncogenesPIK3AP1In silico discovery and modeling of non-coding RNA structure in viruses
Moss WN, Steitz JA. In silico discovery and modeling of non-coding RNA structure in viruses. Methods 2015, 91: 48-56. PMID: 26116541, PMCID: PMC4684774, DOI: 10.1016/j.ymeth.2015.06.015.Peer-Reviewed Original ResearchViral noncoding RNAs: more surprises
Tycowski KT, Guo YE, Lee N, Moss WN, Vallery TK, Xie M, Steitz JA. Viral noncoding RNAs: more surprises. Genes & Development 2015, 29: 567-584. PMID: 25792595, PMCID: PMC4378190, DOI: 10.1101/gad.259077.115.Peer-Reviewed Original ResearchConceptsDiverse biological rolesSmall noncoding RNAsMultitude of functionsHost immune evasionEukaryotic cellsCellular transformationNoncoding RNAsHost counterpartsAnimal virusesBiological roleNcRNAsRNA virusesViral ncRNAsMechanism of actionImmune evasionViral replicationMore surprisesBiogenesisViral persistenceRNAProteinDNAVirusRegulationReplicationEBV Noncoding RNA Binds Nascent RNA to Drive Host PAX5 to Viral DNA
Lee N, Moss WN, Yario TA, Steitz JA. EBV Noncoding RNA Binds Nascent RNA to Drive Host PAX5 to Viral DNA. Cell 2015, 160: 607-618. PMID: 25662012, PMCID: PMC4329084, DOI: 10.1016/j.cell.2015.01.015.Peer-Reviewed Original ResearchConceptsTerminal repeatNascent RNANoncoding RNAsNuclear noncoding RNAB-cell transcription factor PAX5Greater sequence divergenceDNA target sitesTranscription factor Pax5Chromatin localizationTR lociSequence divergenceNascent transcriptsUndescribed functionTranscription factorsLatent EBV genomeRNATarget siteEssential rolePrimate herpesvirusesEBV lytic replicationPAX5Lytic replicationViral DNAEBER2Viral replication
2014
Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function
Guo YE, Riley KJ, Iwasaki A, Steitz JA. Alternative Capture of Noncoding RNAs or Protein-Coding Genes by Herpesviruses to Alter Host T Cell Function. Molecular Cell 2014, 54: 67-79. PMID: 24725595, PMCID: PMC4039351, DOI: 10.1016/j.molcel.2014.03.025.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteBase SequenceCallithrixEnzyme ActivationGene Expression RegulationGPI-Linked ProteinsGRB2 Adaptor ProteinHEK293 CellsHerpesvirus 2, SaimiriineHigh-Throughput Nucleotide SequencingHost-Pathogen InteractionsHumansImmunoprecipitationInterferon-gammaJurkat CellsLectins, C-TypeLymphocyte ActivationMicroRNAsMitogen-Activated Protein KinasesMolecular Sequence DataReceptors, Antigen, T-CellRNA StabilityRNA, UntranslatedRNA, ViralSemaphorinsSequence Analysis, RNASignal TransductionT-LymphocytesTime FactorsTransfectionConceptsMitogen-activated protein kinaseMiR-27Protein coding genesHerpesvirus saimiriHigh-throughput sequencingTCR-induced activationCell functionHSUR 1Γ-herpesvirusesNoncoding RNAsProtein kinaseEctopic expressionOncogenic γ-herpesvirusesTarget genesInduction of CD69MicroRNA-27Key modulatorRNACommon targetAlHV-1GenesCell receptorDiverse strategiesHost T-cell functionCells
2013
RNA families in Epstein–Barr virus
Moss WN, Lee N, Pimienta G, Steitz JA. RNA families in Epstein–Barr virus. RNA Biology 2013, 11: 10-17. PMID: 24441309, PMCID: PMC3929418, DOI: 10.4161/rna.27488.Peer-Reviewed Original ResearchConceptsEpstein-Barr virusFunctional importanceSmall regulatory RNAsNovel Epstein-Barr virusSmall nucleolar RNAsLikely functional importanceInternal ribosomal entry siteRNA-seq studiesHuman γ-herpesvirusEvolutionary conservationNovel ncRNARegulatory RNAsShort intronsRecent bioinformaticsNucleolar RNAsOncogenic typesRNA familiesTumorigenic phenotypeStructured RNAsEBV genomeEBNA1 mRNARepetitive regionsViral latencyHigh abundanceLatency maintenanceGenome-wide analyses of Epstein-Barr virus reveal conserved RNA structures and a novel stable intronic sequence RNA
Moss WN, Steitz JA. Genome-wide analyses of Epstein-Barr virus reveal conserved RNA structures and a novel stable intronic sequence RNA. BMC Genomics 2013, 14: 543. PMID: 23937650, PMCID: PMC3751371, DOI: 10.1186/1471-2164-14-543.Peer-Reviewed Original ResearchConceptsStable intronic sequence RNARNA structureSequence RNAComprehensive genome-wide surveyGenome-wide surveyGenome-wide analysisRNA-seq analysisComparative sequence analysisNon-coding RNAsSecondary structure modelRNA-seq dataRNAz programFunctional RNAsGenomic sequencesImportant human pathogenSequence analysisRNAEBV transcriptomeHuman pathogensHerpesvirus 4Future experimental analysisPotential functionTranscriptomeGenomeEBV genome
2012
AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein-Barr virus
Lee N, Pimienta G, Steitz JA. AUF1/hnRNP D is a novel protein partner of the EBER1 noncoding RNA of Epstein-Barr virus. RNA 2012, 18: 2073-2082. PMID: 23012480, PMCID: PMC3479396, DOI: 10.1261/rna.034900.112.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAptamers, NucleotideAU Rich ElementsBinding, CompetitiveCell Line, TumorHerpesvirus 4, HumanHeterogeneous Nuclear Ribonucleoprotein D0Heterogeneous-Nuclear Ribonucleoprotein DHost-Pathogen InteractionsHumansImmunoprecipitationMutagenesis, InsertionalProtein BindingProtein IsoformsRNA StabilityRNA, ViralConceptsAU-rich elementsProtein partnersAUF1/hnRNP DUntranslated regionBacteriophage MS2 coat proteinNovel protein partnersHigh abundanceElectrophoretic mobility shift assaysEpstein-Barr virusMS2 coat proteinStable isotope labelingMobility shift assaysInteracting proteinMolecular functionsHnRNP DAlternative splicingNoncoding RNAsShift assaysCoat proteinIsotope labelingP40 isoformRNA aptamersRNA 1AUF1UV crosslinkingTracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry
Borah S, Nichols LA, Hassman LM, Kedes DH, Steitz JA. Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry. RNA 2012, 18: 1573-1579. PMID: 22745225, PMCID: PMC3404377, DOI: 10.1261/rna.033126.112.Peer-Reviewed Original ResearchConceptsKaposi's sarcoma-associated herpesvirusSarcoma-associated herpesvirusSubcellular localizationProtein moleculesHigh-throughput approachPAN RNAProtein speciesNoncoding RNAsNuclear RNAProtein C1Imaging Flow CytometryFlow cytometryRNANuclear translocationHigh-throughput applicationsLytic phaseViral RNATranslocationExpressionLocalizationCellsHeterogeneous populationPABPC1CytometryMoleculesEBV and human microRNAs co‐target oncogenic and apoptotic viral and human genes during latency
Riley KJ, Rabinowitz GS, Yario TA, Luna JM, Darnell RB, Steitz JA. EBV and human microRNAs co‐target oncogenic and apoptotic viral and human genes during latency. The EMBO Journal 2012, 31: 2207-2221. PMID: 22473208, PMCID: PMC3343464, DOI: 10.1038/emboj.2012.63.Peer-Reviewed Original ResearchConceptsHuman microRNAsLatent membrane protein 1Viral miRNA functionHigh-throughput sequencingHuman miRNA targetsMiRNA-binding sitesMiRNA functionEBV BHRF1Human genesMiRNA targetsMRNA targetsCellular miRNAsMembrane protein 1MiRNA clusterHuman miRNAsGene expressionCell cycleReporter assaysDistinct binding sitesViral mRNAsMiRNAsLytic genesLytic switchProtein 1EBV latent membrane protein 1
2011
A Viral Nuclear Noncoding RNA Binds Re-localized Poly(A) Binding Protein and Is Required for Late KSHV Gene Expression
Borah S, Darricarrère N, Darnell A, Myoung J, Steitz JA. A Viral Nuclear Noncoding RNA Binds Re-localized Poly(A) Binding Protein and Is Required for Late KSHV Gene Expression. PLOS Pathogens 2011, 7: e1002300. PMID: 22022268, PMCID: PMC3192849, DOI: 10.1371/journal.ppat.1002300.Peer-Reviewed Original ResearchConceptsPAN RNAKaposi's Sarcoma-Associated HerpesvirusNuclear noncoding RNANuclear noncoding RNAsShutoff effectLytic phaseKSHV gene expressionRepertoire of functionsTail of mRNATransient transfection experimentsConsequence of expressionLate viral proteinsNoncoding RNAsExonuclease proteinNuclear RNAProtein C1Translation efficiencyHost mRNAsMRNA stabilityGene expressionUnknown functionTransfection experimentsViral mRNAsPABPC1Binding proteinA Primate Herpesvirus Uses the Integrator Complex to Generate Viral MicroRNAs
Cazalla D, Xie M, Steitz JA. A Primate Herpesvirus Uses the Integrator Complex to Generate Viral MicroRNAs. Molecular Cell 2011, 43: 982-992. PMID: 21925386, PMCID: PMC3176678, DOI: 10.1016/j.molcel.2011.07.025.Peer-Reviewed Original ResearchConceptsEnd processing signalsHerpesvirus saimiriMature viral miRNAsPre-miRNA hairpinsCis-acting elementsMarmoset T cellsIntegrator complexAGO proteinsMiRNA biogenesisMicroprocessor complexU RNAExportin-5Noncoding RNAsViral miRNAsProcessing assaysHost miRNAsDeep sequencingViral noncoding RNAsProtein componentsComplex cleavesHairpin structureHSURsPrimate herpesvirusesMiRNAsRNA
2010
Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix
Mitton-Fry RM, DeGregorio SJ, Wang J, Steitz TA, Steitz JA. Poly(A) Tail Recognition by a Viral RNA Element Through Assembly of a Triple Helix. Science 2010, 330: 1244-1247. PMID: 21109672, PMCID: PMC3074936, DOI: 10.1126/science.1195858.Peer-Reviewed Original ResearchConceptsSarcoma-associated herpesvirusBox H/ACA small nucleolar RNAsMajor-groove triple helixNuclear noncoding RNANuclear retention elementSmall nucleolar RNAsViral RNA elementsRich internal loopTriple helixKaposi's sarcoma-associated herpesvirusPAN RNADeadenylation assaysRNA decayRNA clampNucleolar RNAsNoncoding RNAsNuclear RNATail recognitionRNA elementsFunctional importanceAngstrom resolutionRich loopSecondary structureRNAEne coreNoncoding RNPs of Viral Origin
Steitz J, Borah S, Cazalla D, Fok V, Lytle R, Mitton-Fry R, Riley K, Samji T. Noncoding RNPs of Viral Origin. Cold Spring Harbor Perspectives In Biology 2010, 3: a005165. PMID: 20719877, PMCID: PMC3039937, DOI: 10.1101/cshperspect.a005165.Peer-Reviewed Original Research