2021
Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts
Rosa-Mercado NA, Steitz JA. Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts. Trends In Biochemical Sciences 2021, 47: 206-217. PMID: 34489151, PMCID: PMC8840951, DOI: 10.1016/j.tibs.2021.08.003.Peer-Reviewed Original ResearchConceptsCellular stress responseHuman protein-coding genesStress responseProtein-coding genesDoG inductionNascent mRNAReadthrough transcriptionTranscriptional landscapeDifferent stress conditionsReadthrough transcriptsStress conditionsViral proteinsBiogenesisStress removalGenesTranscriptsCell exposureProduction playTranscriptionRNAProteinMRNAHostProductionHallmark
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 releaseCaution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal
Sabath N, Vilborg A, Steitz JA, Shalgi R. Caution needs to be taken when assigning transcription start sites to ends of protein-coding genes: a rebuttal. Human Genomics 2018, 12: 32. PMID: 29945683, PMCID: PMC6020437, DOI: 10.1186/s40246-018-0164-4.Peer-Reviewed Original ResearchConceptsTranscription start siteTranscriptional readthroughStart siteOsmotic stressProtein-coding genesGenome-wide comparisonEnd of genesStress-mediated inductionMammalian stress responseNIH3T3 mouse cellsDe novo initiationTranscription initiationGene endMammalian cellsLong transcriptsNIH3T3 cellsMouse cellsSimilar transcriptsStress responseTSS-seqHuman cellsReadthroughNovo initiationDramatic inductionStress conditions
2017
Comparative analysis reveals genomic features of stress-induced transcriptional readthrough
Vilborg A, Sabath N, Wiesel Y, Nathans J, Levy-Adam F, Yario TA, Steitz JA, Shalgi R. Comparative analysis reveals genomic features of stress-induced transcriptional readthrough. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e8362-e8371. PMID: 28928151, PMCID: PMC5635911, DOI: 10.1073/pnas.1711120114.Peer-Reviewed Original ResearchConceptsTranscriptional readthroughReadthrough transcriptionGenomic featuresOsmotic stressProtein-coding gene lociHeat shockUnique chromatin signatureGenome-wide mappingOpen chromatin statePolymerase II occupancyNuclear RNA-seqGenome-wide studiesChromatin signaturesChromatin stateNIH 3T3 mouse fibroblast cellsNeighboring genesRNA classesReadthrough transcriptsReadthrough phenomenonRegulated processRNA-seqGene transcriptionGene locusStress responsePotential regulatorSettling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover
Rosa-Mercado NA, Withers JB, Steitz JA. Settling the m6A debate: methylation of mature mRNA is not dynamic but accelerates turnover. Genes & Development 2017, 31: 957-958. PMID: 28637691, PMCID: PMC5495124, DOI: 10.1101/gad.302695.117.Peer-Reviewed Original ResearchConceptsPre-mRNA splicing eventsPost-transcriptional modificationsMRNA biogenesisDifferent subcellular fractionsMRNA biologySplicing eventsMature mRNABiochemical approachesRNA transcriptsPivotal regulatorMethylation levelsHeLa cellsSubcellular fractionsRNA nucleosidesMethylationTranscriptsBiogenesisChromatinSplicingMethyladenosineExonsGenesRNABiologyRegulator
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 analysisDegradationMicroRNAsReadthrough 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 releaseReticulumMechanism
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 transformationViral 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
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 cycleMicroRNAsMiRNAsRNADNAMRNAVirusExpressionInteractionMinireviewDiscoveryVersatile 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 TransductionTime FactorsT-LymphocytesTransfectionConceptsMitogen-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 functionCellsThe 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
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 microRNAMiRNAsMicroRNAsPathwayMicroRNPsGenome-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 genomeThe “Observer Effect” in Genome-wide Surveys of Protein-RNA Interactions
Riley KJ, Steitz JA. The “Observer Effect” in Genome-wide Surveys of Protein-RNA Interactions. Molecular Cell 2013, 49: 601-604. PMID: 23438856, PMCID: PMC3719848, DOI: 10.1016/j.molcel.2013.01.030.Peer-Reviewed Original Research