2022
Joan Heath interviews Suzanne Cory and Joan Steitz: a female perspective of science in the swinging '60s.
Heath J, Cory S, Steitz J. Joan Heath interviews Suzanne Cory and Joan Steitz: a female perspective of science in the swinging '60s. Disease Models & Mechanisms 2022, 15 PMID: 35662325, PMCID: PMC9194481, DOI: 10.1242/dmm.049609.Peer-Reviewed Original ResearchModulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells
Vijayakumar A, Park A, Steitz JA. Modulation of mRNA 3′-End Processing and Transcription Termination in Virus-Infected Cells. Frontiers In Immunology 2022, 13: 828665. PMID: 35222412, PMCID: PMC8866245, DOI: 10.3389/fimmu.2022.828665.Peer-Reviewed Original Research
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 2STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts
Zimmer JT, Rosa-Mercado NA, Canzio D, Steitz JA, Simon MD. STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts. Molecular Cell 2021, 81: 4398-4412.e7. PMID: 34520723, PMCID: PMC9020433, DOI: 10.1016/j.molcel.2021.08.019.Peer-Reviewed Original ResearchConceptsPause releaseRNA polymerase II transcriptsRNA polymerase II moleculesCis-acting DNA elementsTATA box-containing promotersPolymerase II transcriptsPromoter-proximal pausingCritical regulatory functionsTranscriptional regulationRNA turnoverTranscriptional controlDNA elementsTranscriptional shutdownPause sitesHyperosmotic stressRegulatory mechanismsRegulatory functionsPrinciples of regulationHormonal stimuliPausingPremature terminationTranscriptsRegulationWho 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 playTranscriptionRNAProteinMRNAHostProductionHallmarktRNA-like leader-trailer interaction promotes 3′-end maturation of MALAT1
Torabi SF, DeGregorio SJ, Steitz JA. tRNA-like leader-trailer interaction promotes 3′-end maturation of MALAT1. RNA 2021, 27: 1140-1147. PMID: 34253686, PMCID: PMC8457004, DOI: 10.1261/rna.078810.121.Peer-Reviewed Original ResearchStructural analyses of an RNA stability element interacting with poly(A)
Torabi SF, Chen YL, Zhang K, Wang J, DeGregorio SJ, Vaidya AT, Su Z, Pabit SA, Chiu W, Pollack L, Steitz JA. Structural analyses of an RNA stability element interacting with poly(A). Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2026656118. PMID: 33785601, PMCID: PMC8040590, DOI: 10.1073/pnas.2026656118.Peer-Reviewed Original ResearchConceptsRNA stability elementCis-acting RNA elementsGlobal conformational changesRich internal loopCryo-electron microscopyRice transposable elementsDiverse genomesDouble-helical regionsSmall-angle X-ray scatteringEne motifTransposable elementsGlobal structural changesRNA interactionsRNA stabilityBioinformatics studiesRNA elementsStability elementShort helixConformational changesDecay pathwaysInternal loopBiochemical structureTriplex structureBindingMotifRNA stabilization by a poly(A) tail 3′-end binding pocket and other modes of poly(A)-RNA interaction
Torabi SF, Vaidya AT, Tycowski KT, DeGregorio SJ, Wang J, Shu MD, Steitz TA, Steitz JA. RNA stabilization by a poly(A) tail 3′-end binding pocket and other modes of poly(A)-RNA interaction. Science 2021, 371 PMID: 33414189, PMCID: PMC9491362, DOI: 10.1126/science.abe6523.Peer-Reviewed Original ResearchHyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression
Rosa-Mercado NA, Zimmer JT, Apostolidi M, Rinehart J, Simon MD, Steitz JA. Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression. Molecular Cell 2021, 81: 502-513.e4. PMID: 33400923, PMCID: PMC7867636, DOI: 10.1016/j.molcel.2020.12.002.Peer-Reviewed Original ResearchConceptsWidespread transcriptional repressionTranscriptional repressionPol IIIntegrator complex subunitsRNA polymerase IIGenome-wide lossStress-induced redistributionParental genesTranscriptional outputDoG inductionPolymerase IIChIP sequencingHuman cell linesUpstream geneComplex subunitsPolyadenylation factorsTranscription profilesReadthrough transcriptsCatalytic subunitIntegrator activityCellular stressHyperosmotic stressTranscriptional levelTranscription resultsGenes
2019
Increasing gender diversity in the STEM research workforce
Greider CW, Sheltzer JM, Cantalupo NC, Copeland WB, Dasgupta N, Hopkins N, Jansen JM, Joshua-Tor L, McDowell GS, Metcalf JL, McLaughlin B, Olivarius A, O'Shea EK, Raymond JL, Ruebain D, Steitz JA, Stillman B, Tilghman SM, Valian V, Villa-Komaroff L, Wong JY. Increasing gender diversity in the STEM research workforce. Science 2019, 366: 692-695. PMID: 31699926, DOI: 10.1126/science.aaz0649.Peer-Reviewed Original ResearchGender-based harassmentGender-specific barriersAdvancement of womenDomestic laborPolicy changesWomen's abilitySystemic barriersCultural factorsUnequal distributionU.S. institutionsGender diversityResearch institutionsFunding agenciesProfessional focusHarassmentUnconscious biasesResearch fundingResearch workforceInstitutionsCareerSTEM disciplinesResearch careerScientific careerGovernanceSuccessful strategyQuantitative Fluorescence In Situ Hybridization (FISH) and Immunofluorescence (IF) of Specific Gene Products in KSHV-Infected Cells.
Vallery TK, Steitz JA. Quantitative Fluorescence In Situ Hybridization (FISH) and Immunofluorescence (IF) of Specific Gene Products in KSHV-Infected Cells. Journal Of Visualized Experiments 2019 PMID: 31524859, PMCID: PMC6750728, DOI: 10.3791/59697.Peer-Reviewed Original ResearchConceptsRNA FISHSarcoma-associated herpesvirusSpecific RNAViral replication compartmentsSpecific gene productsSitu hybridizationKaposi's sarcoma-associated herpesvirusMultiple cell typesReplication compartmentsGene productsViral genesHost cellsCell typesQuantitative fluorescenceNuclear factoriesFishCell morphologyHuman hostMechanistic insightsSpatiotemporal activityUninfected cellsBehavior of biomoleculesRNAProteinCellsStructural 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 mechanismBiogenesisHow Complementary Targets Expose the microRNA 3′ End for Tailing and Trimming during Target-Directed microRNA Degradation
Pawlica P, Sheu-Gruttadauria J, MacRae IJ, Steitz JA. How Complementary Targets Expose the microRNA 3′ End for Tailing and Trimming during Target-Directed microRNA Degradation. Cold Spring Harbor Symposia On Quantitative Biology 2019, 84: 039321. PMID: 32019864, PMCID: PMC9161719, DOI: 10.1101/sqb.2019.84.039321.Peer-Reviewed Original ResearchTarget-directed miRNA degradationMiRNA 3' endCellular enzymesMiRNA seed sequencesMiRNA complementarityMiRNA decayArgonaute proteinsMicroRNA degradationMiRNA degradationMiRNA 5Posttranscriptional regulationMiRNA targetsCertain transcriptsSeed sequenceExtensive complementarityMolecular mechanismsMessenger RNATranscriptsEnzymeRegulationEnzymatic attackRecent advancesTargetMicroRNAsRNA
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 conditionsKaposi'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 cycleImmunoprecipitation of Tri-methylated Capped RNA.
Hayes KE, Barr JA, Xie M, Steitz JA, Martinez I. Immunoprecipitation of Tri-methylated Capped RNA. Bio-protocol 2018, 8 PMID: 29527542, PMCID: PMC5842925, DOI: 10.21769/bioprotoc.2717.Peer-Reviewed Original ResearchPri-miRNAsCellular quiescenceAlternative miRNA biogenesis pathwaysMiRNA biogenesis pathwayNon-coding RNAsBiogenesis pathwayDNA replicationTotal RNA extractsRNA immunoprecipitationOrgan regenerationRNA extractsFibroblast cellsImmunoprecipitationRNASpecific isolationProteinQuiescenceWound healingImportant roleTrimethylguanosineMicroRNAsAutophagyCytoplasmP27Pathway
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 regulatorNot just Salk.
Greider C, Hopkins N, Steitz J, Amon A, Asai D, Barres B, Bass B, Bassler B, Birgeneau R, Bjorkman P, Botchan M, Brugge J, Cech T, Colwell R, Craig N, deLange T, Eisen M, Gottesman S, Green R, Handelsman J, Kimble J, King MC, Lehmann R, Marder E, Mullins D, O'Shea E, Schmid S, Seydoux G, Spradling A, Storz G, Szostak J, Telesnitsky A, Tilghman S, Tjian R, Vale R, Wolberger C, Zakian V. Not just Salk. Science (New York, N.Y.) 2017, 357: 1105-1106. PMID: 28912235, DOI: 10.1126/science.aao6221.Peer-Reviewed Original Research