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
2017
An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence
Martinez I, Hayes KE, Barr JA, Harold AD, Xie M, Bukhari SIA, Vasudevan S, Steitz JA, DiMaio D. An Exportin-1–dependent microRNA biogenesis pathway during human cell quiescence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e4961-e4970. PMID: 28584122, PMCID: PMC5488920, DOI: 10.1073/pnas.1618732114.Peer-Reviewed Original ResearchConceptsBiogenesis pathwayExportin 1Exportin-5Canonical miRNA biogenesis pathwayCanonical miRNA biogenesisTrimethylguanosine synthase 1MicroRNA biogenesis pathwayMiRNA biogenesis pathwayMiRNA processing pathwayStem cell biologyCellular growth arrestGroup of miRNAsExpression of miRNAsPrimary human fibroblastsMiRNA biogenesisPrimary miRNAsCellular quiescenceTissue homeostasisCell biologyProliferative arrestSpecific miRNAsCell quiescenceGrowth arrestBiogenesisMiRNAs
2016
Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
Pawlica P, Moss WN, Steitz JA. Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region. RNA 2016, 22: 1181-1189. PMID: 27335146, PMCID: PMC4931111, DOI: 10.1261/rna.054817.115.Peer-Reviewed Original ResearchConceptsSmall nuclear RNAMiR-27Nuclear RNAVivo secondary structureBioinformatic structural analysisBinding site sequenceMiRNA degradationU RNARNA functionMutagenic analysisHSUR1Interacting regionsSite sequenceHost microRNAsSecondary structureHerpesvirus saimiriT cell activationOncogenic herpesvirusRNAStructural flexibilityDecreased levelsMutantsStructural analysisDegradationMicroRNAs
2015
A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting
Herbert KM, Sarkar SK, Mills M, De la Herran H, Neuman KC, Steitz JA. A heterotrimer model of the complete Microprocessor complex revealed by single-molecule subunit counting. RNA 2015, 22: 175-183. PMID: 26683315, PMCID: PMC4712668, DOI: 10.1261/rna.054684.115.Peer-Reviewed Original ResearchConceptsPri-miRNA substratesMicroprocessor complexHeterotrimeric complexDeletion constructsSingle-molecule subunit countingRNA-binding proteinFull-length proteinAbsence of RNAStem-loop structureSingle-molecule photobleachingSize exclusion chromatographyPresence of RNARNaseIII enzymesPhotobleaching assaysMicroRNA biogenesisSubunit countingMammalian cellsDroshaDGCR8Fluorescent proteinHuman cellsMultiple copiesRNAProteinExact stoichiometryHerpesvirus saimiri MicroRNAs Preferentially Target Host Cell Cycle Regulators
Guo YE, Oei T, Steitz JA. Herpesvirus saimiri MicroRNAs Preferentially Target Host Cell Cycle Regulators. Journal Of Virology 2015, 89: 10901-10911. PMID: 26292323, PMCID: PMC4621106, DOI: 10.1128/jvi.01884-15.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBlotting, WesternCallithrixCDC2 Protein KinaseCell Cycle ProteinsEndoplasmic Reticulum Chaperone BiPHeat-Shock ProteinsHEK293 CellsHerpesvirus 2, SaimiriineHigh-Throughput Nucleotide SequencingHumansImmunoprecipitationLuciferasesMicroRNAsPhosphorylationRNA, MessengerT-LymphocytesConceptsHost cell cycle regulatorsViral miRNAsCell cycle regulatorsHerpesvirus saimiriMRNA targetsCycle regulatorsProtein-coding genesPre-miRNA hairpinsCross-linking immunoprecipitationGene ontology analysisHigh-throughput sequencingOpen reading frameOncogenic Herpesvirus saimiriCyclin-dependent kinasesP300 transcriptional coactivatorCell cycle progressionKey negative regulatorMarmoset T cellsHITS-CLIPRepresses expressionOntology analysisTranscriptional coactivatorViral life cyclePrimary transcriptCellular transformationThe host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends
Xie M, Zhang W, Shu MD, Xu A, Lenis DA, DiMaio D, Steitz JA. The host Integrator complex acts in transcription-independent maturation of herpesvirus microRNA 3′ ends. Genes & Development 2015, 29: 1552-1564. PMID: 26220997, PMCID: PMC4526738, DOI: 10.1101/gad.266973.115.Peer-Reviewed Original ResearchConceptsEnd processing signalsSmall nuclear RNAProximity ligation assayEnd processingPre-miRNAsHerpesvirus saimiriPre-miRNA hairpinsRNA-protein interactionsSitu proximity ligation assayIntegrator complexMiRNA 3MiRNA biogenesisSnRNA 3Primary miRNAMiRNA hairpinsIntegrator activityNuclear RNASequence downstreamOncogenic γ-herpesvirusesRescue experimentsLigation assayVivo knockdownComplex actsΓ-herpesvirusesHairpinViral 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 persistenceRNAProteinDNAVirusRegulationReplication
2014
Virus 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 cycleMicroRNAsMiRNAsRNADNAMRNAVirusExpressionInteractionMinireviewDiscovery3′-Biotin-tagged microRNA-27 does not associate with Argonaute proteins in cells
Guo YE, Steitz JA. 3′-Biotin-tagged microRNA-27 does not associate with Argonaute proteins in cells. RNA 2014, 20: 985-988. PMID: 24821854, PMCID: PMC4114695, DOI: 10.1261/rna.045054.114.Peer-Reviewed Original ResearchVersatile microRNA biogenesis in animals and their viruses
Xie M, Steitz JA. Versatile microRNA biogenesis in animals and their viruses. RNA Biology 2014, 11: 673-681. PMID: 24823351, PMCID: PMC4156499, DOI: 10.4161/rna.28985.Peer-Reviewed Original ResearchConceptsEssential cellular processesMiRNA regulatory networkPost-transcriptional levelUbiquitous gene regulatorsNon-canonical pathwayMost miRNAsCytoplasmic DicerMicroRNA biogenesisMolecular machineryCellular processesRegulatory networksPrimary transcriptGene regulatorsNuclear DroshaCellular RNABiogenesisDroshaAlternative mechanismFundamental roleCleavage stepMetazoansDicerMiRNAsMicroRNAsMiRNAAlternative 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
Mammalian 5′-Capped MicroRNA Precursors that Generate a Single MicroRNA
Xie M, Li M, Vilborg A, Lee N, Shu MD, Yartseva V, Šestan N, Steitz JA. Mammalian 5′-Capped MicroRNA Precursors that Generate a Single MicroRNA. Cell 2013, 155: 1568-1580. PMID: 24360278, PMCID: PMC3899828, DOI: 10.1016/j.cell.2013.11.027.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArgonaute ProteinsBase SequenceBiosynthetic PathwaysDEAD-box RNA HelicasesGenome-Wide Association StudyGuanosineHumansKaryopherinsMiceMicroRNAsMolecular Sequence DataReceptors, Cytoplasmic and NuclearRibonuclease IIIRNA CapsRNA Polymerase IIRNA, Small InterferingTranscription Termination, GeneticConceptsCap-binding protein eIF4EMiRNA biogenesis pathwayNuclear-cytoplasmic transportGuide strand selectionShRNA expression constructsTranscription start siteBiogenesis pathwayCytoplasmic DicerMicroprocessor complexTranscription terminationProtein eIF4EExportin-5MicroRNA precursorsMiRNA hairpinsPrimary transcriptStrand selectionGene regulatorsStart siteDicer cleavageExpression constructsSingle microRNAMiRNAsMicroRNAsPathwayMicroRNPsPhosphorylation of DGCR8 Increases Its Intracellular Stability and Induces a Progrowth miRNA Profile
Herbert KM, Pimienta G, DeGregorio SJ, Alexandrov A, Steitz JA. Phosphorylation of DGCR8 Increases Its Intracellular Stability and Induces a Progrowth miRNA Profile. Cell Reports 2013, 5: 1070-1081. PMID: 24239349, PMCID: PMC3892995, DOI: 10.1016/j.celrep.2013.10.017.Peer-Reviewed Original ResearchConceptsMicroprocessor complexRNA-binding proteinRNase III enzymeInhibition of phosphatasesStem-loop structureERK/MAPKSpecific processing activityMiRNA expression profilesExtracellular cuesMiRNA biogenesisDrosha proteinPhosphorylation sitesPrimary miRNAMammalian cellsProtein stabilityExpression profilesDGCR8Intracellular stabilityHeLa cellsCellular levelMiRNA profilesPhosphorylationMRNA levelsProteinCells
2012
Association of Argonaute proteins and microRNAs can occur after cell lysis
Riley KJ, Yario TA, Steitz JA. Association of Argonaute proteins and microRNAs can occur after cell lysis. RNA 2012, 18: 1581-1585. PMID: 22836356, PMCID: PMC3425773, DOI: 10.1261/rna.034934.112.Peer-Reviewed Original ResearchConceptsHuman AgosMiRNA-protein complexesMicroRNA target identificationDirect mRNA targetsCore protein componentsArgonaute proteinsAGO proteinsMRNA targetsImmunoprecipitation experimentsProtein componentsMiRNA mimicsRNAEndogenous interactionCell lysisTarget identificationImmunopurification techniquesGlobal analysisProteinInteraction artifactsOrigin of interactionsExperimental approachArgonauteVivoAgoMiRNAsEBV 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 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 herpesvirusesMiRNAsRNAPosttranscriptional 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
miR-29 and miR-30 regulate B-Myb expression during cellular senescence
Martinez I, Cazalla D, Almstead LL, Steitz JA, DiMaio D. miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 108: 522-527. PMID: 21187425, PMCID: PMC3021067, DOI: 10.1073/pnas.1017346108.Peer-Reviewed Original ResearchConceptsB-myb expressionCellular senescenceMiR-30MiR-29Reporter constructsEndogenous B-MybMajor tumor suppressor mechanismTumor suppressor mechanismIrreversible growth arrestMicroRNA familiesMutant 3'UTRCellular DNA synthesisB-MybReplicative senescenceCompensatory mutationsGrowth arrestMutant sitesRb pathwaySenescenceSuppressor mechanismDNA synthesisRepressionInhibits senescenceExpressionMutationsNoncoding 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