2019
Structural Basis for Target-Directed MicroRNA Degradation
Sheu-Gruttadauria J, Pawlica P, Klum SM, Wang S, Yario TA, Schirle Oakdale NT, Steitz JA, MacRae IJ. Structural Basis for Target-Directed MicroRNA Degradation. Molecular Cell 2019, 75: 1243-1255.e7. PMID: 31353209, PMCID: PMC6754277, DOI: 10.1016/j.molcel.2019.06.019.Peer-Reviewed Original ResearchConceptsTarget-directed miRNA degradationMiRNA 3' endMicroRNA degradationMiRNA degradationHuman Ago2MiRNA activityMiRNA stabilityStructural basisGene expressionTarget RNALinker flexibilityMiRNAsEnd displaysFlexible linkerRNAKey determinantArgonauteHAgo2Enzymatic attackAgo2DegradationDuplexMicroRNAsMiRNAIsoformsIdiosyncrasies 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 release
2016
Readthrough transcription: How are DoGs made and what do they do?
Vilborg A, Steitz JA. Readthrough transcription: How are DoGs made and what do they do? RNA Biology 2016, 14: 632-636. PMID: 26861889, PMCID: PMC5449079, DOI: 10.1080/15476286.2016.1149680.Peer-Reviewed Original ResearchConceptsDoG inductionDownstream of genesMammalian gene expressionLevel of transcriptionPervasive transcriptionIntergenic transcriptionTranscription terminationPossible molecular mechanismsTranscriptional readthroughOsmotic stressGene expressionMolecular mechanismsEndoplasmic reticulumTranscriptionIP3 receptorOutstanding questionsTranscriptsBiogenesisGenomeInductionReadthroughGenesCalcium releaseReticulumMechanismEBV 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
2014
RNA editing, epitranscriptomics, and processing in cancer progression
Witkin KL, Hanlon SE, Strasburger JA, Coffin JM, Jaffrey SR, Howcroft TK, Dedon PC, Steitz JA, Daschner PJ, Read-Connole E. RNA editing, epitranscriptomics, and processing in cancer progression. Cancer Biology & Therapy 2014, 16: 21-27. PMID: 25455629, PMCID: PMC4622672, DOI: 10.4161/15384047.2014.987555.Peer-Reviewed Original ResearchConceptsRNA modificationsRNA editingNetworks of RNAsTRNA base modificationsEpitranscriptomic RNA modificationsNuclear-cytoplasmic transportCancer progressionCellular stress pathwaysPrimary RNA sequenceRNA processingRNA splicingMRNA translationRNA interferenceRNA moleculesRegulated cleavageGene expressionCancer biologistsRNA sequencesBase modificationsCancer initiationCancer biologyStress pathwaysEnvironmental conditionsRNAEnzymatic pathwaysVirus Meets Host MicroRNA: the Destroyer, the Booster, the Hijacker
Guo YE, Steitz JA. Virus Meets Host MicroRNA: the Destroyer, the Booster, the Hijacker. Molecular And Cellular Biology 2014, 34: 3780-3787. PMID: 25047834, PMCID: PMC4187717, DOI: 10.1128/mcb.00871-14.Peer-Reviewed Original ResearchConceptsKey regulatory stepSmall noncoding RNAsVirus-host interactionsViral life cycleNoncoding RNAsCellular miRNAsMiRNA interactionsRegulatory stepGene expressionProtein productionHost microRNAsRNA virusesRecent discoveryLife cycleMicroRNAsMiRNAsRNADNAMRNAVirusExpressionInteractionMinireviewDiscoveryNuclear Translocation and Regulation of Intranuclear Distribution of Cytoplasmic Poly(A)-Binding Protein Are Distinct Processes Mediated by Two Epstein Barr Virus Proteins
Park R, El-Guindy A, Heston L, Lin SF, Yu KP, Nagy M, Borah S, Delecluse HJ, Steitz J, Miller G. Nuclear Translocation and Regulation of Intranuclear Distribution of Cytoplasmic Poly(A)-Binding Protein Are Distinct Processes Mediated by Two Epstein Barr Virus Proteins. PLOS ONE 2014, 9: e92593. PMID: 24705134, PMCID: PMC3976295, DOI: 10.1371/journal.pone.0092593.Peer-Reviewed Original ResearchConceptsHost gene expressionIntranuclear distributionZEBRA mutantsReplication proteinsNuclear translocationGene expressionEssential replication proteinViral replication proteinsDownstream viral genesViral replication compartmentsLytic replicationNew protein synthesisBZIP proteinsGlobal shutoffViral alkaline nucleaseReplication compartmentsPABPCEssential functionsEpstein-Barr virus proteinsHost shutoffViral genesLytic programProtein synthesisBinding proteinProteinThe Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones
Cech TR, Steitz JA. The Noncoding RNA Revolution—Trashing Old Rules to Forge New Ones. Cell 2014, 157: 77-94. PMID: 24679528, DOI: 10.1016/j.cell.2014.03.008.Peer-Reviewed Original ResearchConceptsBiological functionsRNA-protein complexesLevel of transcriptionForeign nucleic acidsMost ncRNAsLong ncRNAsNcRNA researchRNA processingGenome rearrangementsNucleic acidsNoncoding RNAsGene expressionRNA structureNcRNAsBase pairingDNA synthesisRemarkable varietySnoRNPsRiboswitchGenomeSnRNPsRNAsRibosomesTranscriptionTelomerase
2012
EBV 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 proteinPosttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA–protein complexes (microRNPs)
Mortensen RD, Serra M, Steitz JA, Vasudevan S. Posttranscriptional activation of gene expression in Xenopus laevis oocytes by microRNA–protein complexes (microRNPs). Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 8281-8286. PMID: 21536868, PMCID: PMC3100953, DOI: 10.1073/pnas.1105401108.Peer-Reviewed Original ResearchConceptsMicroRNA–protein complexesProtein kinase AIIXenopus laevis oocytesImmature Xenopus laevis oocytesGene expression activationMammalian cell linesLaevis oocytesHuman Ago2Target reporterMammalian cellsExpression activationMyt1 kinaseGene expressionPosttranscriptional activationRegulated expressionSpecific mRNAsPhysiological relevanceQuiescent cellsMicroRNAsOocyte stateCell linesOocytesReporterCAMP levelsExpression
2010
Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA
Cazalla D, Yario T, Steitz JA. Down-Regulation of a Host MicroRNA by a Herpesvirus saimiri Noncoding RNA. Science 2010, 328: 1563-1566. PMID: 20558719, PMCID: PMC3075239, DOI: 10.1126/science.1187197.Peer-Reviewed Original ResearchConceptsHSURs 1Noncoding RNAsHost cell gene expressionMiR-27Binding-dependent mannerPotential binding sitesMiRNA pathwayHost cell microRNAsCoimmunoprecipitation experimentsEctopic expressionTarget genesTransient knockdownGene expressionUnknown functionHost microRNAsViral strategiesDown regulationBinding sitesMiRNAsMicroRNAsRNAExpressionCellsT cellsNcRNADown-Regulation of a Host microRNA by a Viral Noncoding RNA
Cazalla D, Steitz JA. Down-Regulation of a Host microRNA by a Viral Noncoding RNA. Cold Spring Harbor Symposia On Quantitative Biology 2010, 75: 321-324. PMID: 21139068, PMCID: PMC5647998, DOI: 10.1101/sqb.2010.75.009.Peer-Reviewed Original ResearchConceptsHerpesvirus saimiriNoncoding RNAsHost cell gene expressionMiR-27Binding-dependent mannerAU-rich elementsViral noncoding RNAMarmoset T cellsMiRNA pathwayHost cell microRNAsViral life cycleConserved sequencesEctopic expressionMammalian virusesTarget genesTransient knockdownMutational analysisGene expressionHost microRNAsHSUR1Viral strategiesBase pairingDown regulationPrimate herpesvirusesLytic phase
2009
Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function
Pawlicki JM, Steitz JA. Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function. Trends In Cell Biology 2009, 20: 52-61. PMID: 20004579, PMCID: PMC2821161, DOI: 10.1016/j.tcb.2009.10.004.Peer-Reviewed Original ResearchConceptsMature messenger RNAGene expressionRNA polymerase II transcriptsProtein-coding genesPolymerase II transcriptsRNA polymerase IIMessenger RNAPre-messenger RNARNA processing reactionsCotranscriptional eventsPolymerase IIProcessing eventsProcessing reactionsExtensive molecular interactionsEarly stepsTranscriptsRNAExquisite couplingMolecular interactionsMicroRNAsExpressionNuclear networkCrucial roleFinal fateSplicingmiRNPs: versatile regulators of gene expression in vertebrate cells1
Steitz JA, Vasudevan S. miRNPs: versatile regulators of gene expression in vertebrate cells1. Biochemical Society Transactions 2009, 37: 931-935. PMID: 19754429, DOI: 10.1042/bst0370931.Peer-Reviewed Original ResearchConceptsPost-transcriptional controlAssociation of Ago2Role of miRNAsImmature Xenopus oocytesTNFalpha AREProtein FXR1Contact-inhibited cellsTranslational regulationTranslation activationVersatile regulatorsTranslational efficiencyNegative regulatorGene expressionSpecific miRNACell cycleEffector moleculesCell growthXenopus oocytesAgo2FXR1Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: Processing at transcription sites or accumulation in SC35 foci
Pawlicki JM, Steitz JA. Subnuclear compartmentalization of transiently expressed polyadenylated pri-microRNAs: Processing at transcription sites or accumulation in SC35 foci. Cell Cycle 2009, 8: 345-356. PMID: 19177009, PMCID: PMC3004524, DOI: 10.4161/cc.8.3.7494.Peer-Reviewed Original ResearchConceptsPri-miRNA processingPri-miRNAsTranscription sitesPrimary miRNA transcriptsPri-miRNA transcriptsPre-miRNA hairpinsRNA polymerase IIASF/SF2Splicing factor SC35Target messenger RNAsNumber of proteinsMiRNA biogenesisMiRNA transcriptsNuclear organizationMRNA metabolismPolymerase IINuclear fociProlyl isomeraseFactor SC35Subnuclear compartmentalizationPri-microRNAsMammalian cellsSC35 domainsGene expressionSC35
2008
Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production
Pawlicki JM, Steitz JA. Primary microRNA transcript retention at sites of transcription leads to enhanced microRNA production. Journal Of Cell Biology 2008, 182: 61-76. PMID: 18625843, PMCID: PMC2447899, DOI: 10.1083/jcb.200803111.Peer-Reviewed Original ResearchMeSH KeywordsChromatinExonsHeLa CellsHumansIntronsMicroRNAsMRNA Cleavage and Polyadenylation FactorsNuclear ProteinsPolyadenylationRegulatory Sequences, Nucleic AcidRibonucleoproteinsRNA Polymerase IIIRNA Processing, Post-TranscriptionalRNA TransportRNA, MessengerRNA, ViralSequence DeletionSerine-Arginine Splicing FactorsSubcellular FractionsTranscription, GeneticConceptsPri-miRNAsTranscription sitesEndogenous pri-miRNAsPrimary miRNA transcriptsPri-miRNA processingSplicing factor SC35Viral RNA elementsHigh nuclear levelsMiRNA biogenesisMiRNA transcriptionMiRNA transcriptsNuclear stepsPrecursor miRNAsNuclear fociFactor SC35MicroRNA productionRNA elementsGene expressionTranscription leadNuclear fractionNuclear levelsTranscriptionMiRNAsProcessing signalsBiogenesis
2007
Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation
Vasudevan S, Tong Y, Steitz JA. Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation. Science 2007, 318: 1931-1934. PMID: 18048652, DOI: 10.1126/science.1149460.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsArgonaute ProteinsBase PairingCell CycleCell LineCell ProliferationComputational BiologyEukaryotic Initiation Factor-2Gene Expression RegulationHeLa CellsHMGA2 ProteinHumansInterphaseMicroRNAsProtein BiosynthesisRibonucleoproteinsRNA-Binding ProteinsRNA, MessengerTransfectionTumor Necrosis Factor-alphaUp-RegulationConceptsAU-rich elementsCell cycle arrestCycle arrestUntranslated regionMental retardation-related protein 1MicroRNA target sitesMicroRNA let-7Messenger RNA (mRNA) 3' untranslated regionsRegulates TranslationTranslation regulationTarget mRNAsGene expressionCell cycleCommon functionProtein 1ArgonauteTarget siteActivation signalsRepressionTumor necrosis factor-alpha mRNAMRNARegulationActivationArrestMicroRNPsAU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2
Vasudevan S, Steitz JA. AU-Rich-Element-Mediated Upregulation of Translation by FXR1 and Argonaute 2. Cell 2007, 128: 1105-1118. PMID: 17382880, PMCID: PMC3430382, DOI: 10.1016/j.cell.2007.01.038.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsArgonaute ProteinsCell CycleCell LineChromatography, AffinityCulture Media, Serum-FreeEukaryotic Initiation Factor-2Genes, ReporterHumansLuciferases, FireflyMonocytesPeptide Initiation FactorsPolyribosomesProtein BiosynthesisRegulatory Sequences, Ribonucleic AcidRibonucleoproteinsRNA-Binding ProteinsSerumTumor Necrosis Factor-alphaUp-RegulationConceptsAU-rich elementsArgonaute 2Posttranscriptional regulatory systemsAffinity purification methodShRNA knockdown experimentsCell cycle arrestHuman cell linesTranslation activationRegulatory signalsMRNA stabilityGene expressionSerum starvationAU-RichFXR1Activation roleRegulatory systemProtein 1Cell linesMRNA levelsNew insightsDevelopmental consequencesTranslation conditionsUpregulationDirect evidencePurification method