2025
Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries
Mustafa A, Davlidova S, Abidi S, Begimbetova D, Heimer R, Vermund S, Ali S. Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries. BMJ Open Gastroenterology 2025, 12: e001657. PMID: 39848793, PMCID: PMC11758705, DOI: 10.1136/bmjgast-2024-001657.Peer-Reviewed Original ResearchConceptsResistance-associated substitutionsResistance to daclatasvirHepatitis C virusEffective treatment of hepatitis C virusPresence of resistance-associated substitutionsPrevalence of HCV genotype 1bPrevalence of resistance-associated substitutionsC virusNS3 resistance-associated substitutionsNS5B resistance-associated substitutionsEmergence of resistance-associated substitutionsNS5A resistance-associated substitutionsTreatment of hepatitis C virusPrevalence of HCV genotypesDirect-acting antiviralsPrevalence of genotypesEffective treatment regimenHCV genotype 1bHCV-infected individualsSequences of hepatitis C virusTreatment regimenHCV genotypesGenotype 1bGenotype 3aEffective treatment
2024
DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Ren X, Liu Q, Zhou P, Zhou T, Wang D, Mei Q, Flavell R, Liu Z, Li M, Pan W, Zhu S. DHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells. Nature Communications 2024, 15: 3080. PMID: 38594251, PMCID: PMC11004185, DOI: 10.1038/s41467-024-47235-2.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseIntestinal stem cellsIntestinal epithelial cellsEpithelial homeostasisSusceptibility to experimental colitisIncreased susceptibility to experimental colitisImpaired ISC functionStem cellsEpithelial barrier dysfunctionGenomic instabilityInflammatory bowel disease patientsPathogenesis of inflammatory bowel diseaseR-loop-mediated genome instabilityHallmarks of inflammatory bowel diseaseContinuous self-renewalBarrier dysfunctionExperimental colitisCrypt destructionEpithelial cellsInflammatory responseSelf-renewalBowel diseaseRisk factorsIntestinal epitheliumProtein levelsTargeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
2023
RIG-I recognizes metabolite-capped RNAs as signaling ligands
Schweibenz B, Solotchi M, Hanpude P, Devarkar S, Patel S. RIG-I recognizes metabolite-capped RNAs as signaling ligands. Nucleic Acids Research 2023, 51: 8102-8114. PMID: 37326006, PMCID: PMC10450190, DOI: 10.1093/nar/gkad518.Peer-Reviewed Original ResearchMeSH KeywordsDEAD Box Protein 58DEAD-box RNA HelicasesHumansImmunity, InnateInterferonsLigandsRNA CapsRNA, Double-StrandedRNA, ViralSignal TransductionConceptsRIG-IRNA endsRIG-I signaling pathwayIn vitro transcriptionRIG-I signalingDouble-stranded RNAInnate antiviral immune responseInterferon responseReceptor RIG-ICellular signaling assaysCapped RNACellular rolesPathogenic RNAsViral genomeEndogenous mRNAReplication intermediatesM7GSignaling ligandsImmune responseInnate immune receptor RIG-ISignaling pathwayRNASignaling assaysATPase activityAntiviral immune response
2022
An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity
Li D, Yang J, Malik V, Huang Y, Huang X, Zhou H, Wang J. An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity. Nucleic Acids Research 2022, 50: 12462-12479. PMID: 36416264, PMCID: PMC9757061, DOI: 10.1093/nar/gkac1084.Peer-Reviewed Original ResearchMeSH KeywordsDEAD-box RNA HelicasesEmbryonic Stem CellsEukaryotic Initiation Factor-4ARNA InterferenceRNA, MessengerConceptsExon junction complexRNA helicaseRNA interferenceEmbryonic stem cellsPost-transcriptionallyEmbryonic stem cell identityEfficient nuclear exportRNA interference screenCell cycle progression of ESCsPost-transcriptional controlCell cycle regulationStem cell identityCell cycle progressionMaintenance of embryonic stem cellsStem cell pluripotencyLoss of pluripotencyRNA metabolismDEAD-boxCell cycle dysregulationCell identityCycle regulationCell pluripotencyCell cyclePluripotency controlCyclin B1The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands
Wang W, Pyle AM. The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands. Molecular Cell 2022, 82: 4131-4144.e6. PMID: 36272408, PMCID: PMC9707737, DOI: 10.1016/j.molcel.2022.09.029.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsDEAD Box Protein 58DEAD-box RNA HelicasesImmunity, InnateLigandsRNA, Double-StrandedRNA, ViralConceptsRNA moleculesRNA ligandsHigh-resolution cryo-EM structuresCryo-EM structureDouble-stranded RNARIG-I receptorInduction of autoimmunityViral RNA moleculesAutoinhibited conformationInnate immune receptorsHost RNARelated RNAProtein foldsMolecular basisUnique molecular featuresHigh-affinity conformationAntiviral sensingHost cellsRNA virusesRNA releaseImmune receptorsRNAViral RNAExquisite selectivityMolecular featuresThe intrinsically disordered CARDs‐Helicase linker in RIG‐I is a molecular gate for RNA proofreading
Schweibenz B, Devarkar S, Solotchi M, Craig C, Zheng J, Pascal B, Gokhale S, Xie P, Griffin P, Patel S. The intrinsically disordered CARDs‐Helicase linker in RIG‐I is a molecular gate for RNA proofreading. The EMBO Journal 2022, 41: embj2021109782. PMID: 35437807, PMCID: PMC9108607, DOI: 10.15252/embj.2021109782.Peer-Reviewed Original ResearchMeSH KeywordsDEAD Box Protein 58DEAD-box RNA HelicasesDNA HelicasesImmunity, InnateProtein Structure, TertiaryRNA, Double-StrandedRNA, ViralConceptsC-terminal domainNon-specific RNAHelicase domainRIG-IRIG-I C-terminal domainReceptor RIG-IRNA proofreadingRNA specificityHelicaseProofreading mechanismInnate immune receptor RIG-IRNAViral RNANovel targetProofreadingAberrant immune responseNegative charge regionViral infectionImmune responseHEL1DomainThe nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release
Gray S, Cao W, Montpetit B, De La Cruz EM. The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release. Nucleic Acids Research 2022, 50: 3998-4011. PMID: 35286399, PMCID: PMC9023272, DOI: 10.1093/nar/gkac164.Peer-Reviewed Original ResearchConceptsNuclear pore complexRNA exportDEAD-box protein Dbp5ATPase cycleDbp5's ATPase activityDEAD (Asp-Glu-Ala-Asp) box protein 5Pore complexDbp5ATP bindingATPase cyclingNucleotide stateCytoplasmic faceGle1Pool of ATPADP-PiGene expressionProtein 5Mechanistic understandingNucleoporinsNup159ATPase activityATP dissociationATPPi releasePi release rate
2021
The molecular mechanism of RIG‐I activation and signaling
Thoresen D, Wang W, Galls D, Guo R, Xu L, Pyle AM. The molecular mechanism of RIG‐I activation and signaling. Immunological Reviews 2021, 304: 154-168. PMID: 34514601, PMCID: PMC9293153, DOI: 10.1111/imr.13022.Peer-Reviewed Original ResearchMeSH KeywordsDEAD-box RNA HelicasesImmunity, InnateInterferon-Induced Helicase, IFIH1RNA, Double-StrandedRNA, ViralSignal TransductionConceptsRIG-I activationTranscription of interferonEvolutionary implicationsAdapter proteinHost RNAPathogenic RNAsPattern recognition receptorsCell biologyInactive conformationMolecular mechanismsRNA virusesRole of RIGRNA duplexesInitial RNARNAStructural determinantsRecognition receptorsInnate immunityViral RNAInterferon expressionImportant receptorViral pathogensCellular spaceMolecular featuresReceptorsInsights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3)
Li K, Zheng J, Wirawan M, Trinh NM, Fedorova O, Griffin PR, Pyle AM, Luo D. Insights into the structure and RNA-binding specificity of Caenorhabditis elegans Dicer-related helicase 3 (DRH-3). Nucleic Acids Research 2021, 49: 9978-9991. PMID: 34403472, PMCID: PMC8464030, DOI: 10.1093/nar/gkab712.Peer-Reviewed Original ResearchConceptsC-terminal domainN-terminal domainDRH-3RNA interferenceTandem caspase activationSimilar domain architectureEndogenous RNAi pathwaysRNA helicase familyDouble-stranded RNACARDs of RIGUnique structural dynamicsGermline developmentEvolutionary divergenceChromosome segregationRNAi pathwayCaenorhabditis elegansDomain architectureHelicase familyCaspase activationDistinct foldsRecruitment domainMolecular understandingRLR familyRNA duplexesRNA
2020
DEAD-box RNA helicase protein DDX21 as a prognosis marker for early stage colorectal cancer with microsatellite instability
Tanaka A, Wang J, Shia J, Zhou Y, Ogawa M, Hendrickson R, Klimstra D, Roehrl M. DEAD-box RNA helicase protein DDX21 as a prognosis marker for early stage colorectal cancer with microsatellite instability. Scientific Reports 2020, 10: 22085. PMID: 33328538, PMCID: PMC7745018, DOI: 10.1038/s41598-020-79049-9.Peer-Reviewed Original ResearchConceptsStage colorectal cancerLate stage colorectal cancerEarly stage colorectal cancerColorectal cancerProtein expressionMicrosatellite instabilityAssociated with longer survivalDisease-free survivalTumor cell nucleiKaplan-Meier analysisColorectal cancer casesNon-mucinous histologyPatient clinical outcomesColorectal cancer cohortEarly stage cancerMismatch repair statusTumor gradeTumor locationBenign mucosaCancer immunityClinicopathological featuresPrognostic markerClinical outcomesLonger survivalCancer casesCytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients
Darbinyan A, Morotti R, Cai G, Prasad ML, Christison‐Lagay E, Dinauer C, Adeniran AJ. Cytomorphologic features of thyroid disease in patients with DICER1 mutations: A report of cytology–histopathology correlation in 7 patients. Cancer Cytopathology 2020, 128: 746-756. PMID: 32897650, DOI: 10.1002/cncy.22329.Peer-Reviewed Original ResearchConceptsDICER1 mutationsThyroid diseaseThyroid carcinomaScreening of patientsFine-needle aspiration samplesMonitoring of patientsDiagnostic cytologic featuresPapillary thyroid carcinomaGermline DICER1 mutationsThyroid fine-needle aspiration samplesFNA evaluationUndetermined significanceDifferent somatic variantsThyroid cancerScant colloidNeoplastic lesionsHistopathological analysisCytomorphologic featuresDICER1 syndromeModerate cellularityCytologic featuresFollicular carcinomaFollicular lesionsInconspicuous nucleoliFollicular neoplasmMIWI prevents aneuploidy during meiosis by cleaving excess satellite RNA
Hsieh C, Xia J, Lin H. MIWI prevents aneuploidy during meiosis by cleaving excess satellite RNA. The EMBO Journal 2020, 39: embj2019103614. PMID: 32677148, PMCID: PMC7429737, DOI: 10.15252/embj.2019103614.Peer-Reviewed Original ResearchConceptsChromosome misalignmentSatellite RNAKinetochore assemblySatellite repeatsWild-type spermatocytesPericentromeric satellite repeatsFaithful chromosome segregationProper kinetochore assemblyChromosome mis-segregationPost-transcriptional regulationPiRNA biogenesisMeiotic functionsPIWI proteinsChromosome segregationMis-segregationMurine memberElevated aneuploidyMale meiosisPrevents aneuploidyDicer cleavageMIWIMetaphase IRNA fragmentsMeiosisRNAIn vivo modeling of metastatic human high-grade serous ovarian cancer in mice
Kim O, Park EY, Klinkebiel DL, Pack SD, Shin YH, Abdullaev Z, Emerson RE, Coffey DM, Kwon SY, Creighton CJ, Kwon S, Chang EC, Chiang T, Yatsenko AN, Chien J, Cheon DJ, Yang-Hartwich Y, Nakshatri H, Nephew KP, Behringer RR, Fernández FM, Cho CH, Vanderhyden B, Drapkin R, Bast RC, Miller KD, Karpf AR, Kim J. In vivo modeling of metastatic human high-grade serous ovarian cancer in mice. PLOS Genetics 2020, 16: e1008808. PMID: 32497036, PMCID: PMC7297383, DOI: 10.1371/journal.pgen.1008808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorChromosomal InstabilityCystadenocarcinoma, SerousDEAD-box RNA HelicasesDisease Models, AnimalDNA RepairDrug Resistance, NeoplasmDrug Screening Assays, AntitumorFeasibility StudiesFemaleHumansMiceMice, KnockoutMutationNeoplasm GradingNeoplasm MetastasisOvarian NeoplasmsPeritoneal NeoplasmsPrimary Cell CulturePTEN PhosphohydrolaseRibonuclease IIITumor Suppressor Protein p53ConceptsHigh-grade serous carcinomaHuman HGSCHigh-grade serous ovarian cancerSerous ovarian cancerOvarian cancerPeritoneal metastasisHuman high-grade serous ovarian cancerMetastatic ovarian cancerOvarian cancer typesHuman cancer metastasisHuman cancer mortalityHemorrhagic ascitesClinical metastasisHistopathological similaritiesSerous carcinomaCancer mortalityFallopian tubeMurine modelPeritoneal cavityMouse modelPotential therapyMouse deathMetastasisCancer typesCancer metastasis
2019
Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti
Göertz GP, van Bree JWM, Hiralal A, Fernhout BM, Steffens C, Boeren S, Visser TM, Vogels CBF, Abbo SR, Fros JJ, Koenraadt CJM, van Oers MM, Pijlman GP. Subgenomic flavivirus RNA binds the mosquito DEAD/H-box helicase ME31B and determines Zika virus transmission by Aedes aegypti. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 19136-19144. PMID: 31488709, PMCID: PMC6754610, DOI: 10.1073/pnas.1905617116.Peer-Reviewed Original ResearchConceptsSubgenomic flavivirus RNAInfectious blood mealZika virusMosquito infectionWild-type Zika virusesFlavivirus RNAMosquito midgut barrierArthropod-borne flavivirusZika virus transmissionBlood mealGlobal human health threatMosquito cell culturesZIKV infectionMosquito salivaIntrathoracic injectionViral Small Interfering RNAsInfected mosquitoesViral titersAntiviral activityFlavivirus replicationFlavivirus transmissionMidgut barrierHealth threatInfectionInfected cellsCooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer
Craig M, Kaveh K, Woosley A, Brown AS, Goldman D, Eton E, Mehta RM, Dhawan A, Arai K, Rahman MM, Chen S, Nowak MA, Goldman A. Cooperative adaptation to therapy (CAT) confers resistance in heterogeneous non-small cell lung cancer. PLOS Computational Biology 2019, 15: e1007278. PMID: 31449515, PMCID: PMC6709889, DOI: 10.1371/journal.pcbi.1007278.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCoculture TechniquesComputational BiologyComputer SimulationCRISPR-Cas SystemsDEAD-box RNA HelicasesDrug Resistance, MultipleDrug Resistance, NeoplasmHumansLung NeoplasmsModels, BiologicalMutationRibonuclease IIIConceptsCancer cellsCell state transitionsWild-type cellsCooperative adaptationNon-small cell lung cancer cellsInterspecies competitionCell lung cancer cellsCRISPR/Drug-sensitive cellsLung cancer cellsNSCLC patient samplesDruggable targetsDrug pressureMutantsFlow cytometry dataPhenotypic heterogeneitySensitive cellsTowards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs
Le-Niculescu H, Roseberry K, Levey D, Rogers J, Kosary K, Prabha S, Jones T, Judd S, McCormick M, Wessel A, Williams A, Phalen P, Mamdani F, Sequeira A, Kurian S, Niculescu A. Towards precision medicine for stress disorders: diagnostic biomarkers and targeted drugs. Molecular Psychiatry 2019, 25: 918-938. PMID: 30862937, PMCID: PMC7192849, DOI: 10.1038/s41380-019-0370-z.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultbeta 2-MicroglobulinBiomarkersDEAD-box RNA HelicasesFemaleGene ExpressionHumansMaleMental DisordersMiddle AgedMolecular Targeted TherapyNogo ProteinsPrecision MedicinePredictive Value of TestsProto-Oncogene ProteinsReceptors, ImmunologicStress, PsychologicalTacrolimus Binding ProteinsTelomere HomeostasisConceptsPredictive biomarkersGene expression biomarkersTelomere lengthBlood gene expression biomarkersPossible new drug candidateStress disorderPsychological stressFuture psychiatric hospitalizationsVisual analog scaleHigh-risk groupSimple visual analog scaleDrug repurposing analysisExpression biomarkersGene expression signaturesAnalog scaleAdverse outcomesCalcium folinateCohort designHormonal changesPsychiatric hospitalizationDecreased qualityBiomarker findingsPsychiatric disordersPsychiatric patientsPatient stratification
2018
RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization
Devarkar S, Schweibenz B, Wang C, Marcotrigiano J, Patel S. RIG-I Uses an ATPase-Powered Translocation-Throttling Mechanism for Kinetic Proofreading of RNAs and Oligomerization. Molecular Cell 2018, 72: 355-368.e4. PMID: 30270105, PMCID: PMC6434538, DOI: 10.1016/j.molcel.2018.08.021.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAdenosine TriphosphateAortic DiseasesCell LineDEAD Box Protein 58DEAD-box RNA HelicasesDental Enamel HypoplasiaFemaleHEK293 CellsHumansHydrolysisKineticsMetacarpusMuscular DiseasesOdontodysplasiaOsteoporosisProtein BindingReceptors, Antigen, T-CellReceptors, ImmunologicRibosomesRNARNA, Double-StrandedSignal TransductionVascular CalcificationConceptsRIG-ISelf-RNARNA discriminationMechanism of RIG-I activationRIG-I oligomerizationC-terminal domainActivation of RIG-IRIG-I activationTransient-state kineticsAutoinhibited stateBind ATPATP bindingDNA polymeraseDsRNAOligomeric complexesConstitutive signalingKinetic proofreadingStem regionATPase activityT cell receptorRNACell receptorsFast off rateATPTranslocationNup159 Weakens Gle1 Binding to Dbp5 But Does Not Accelerate ADP Release
Wong EV, Gray S, Cao W, Montpetit R, Montpetit B, De La Cruz EM. Nup159 Weakens Gle1 Binding to Dbp5 But Does Not Accelerate ADP Release. Journal Of Molecular Biology 2018, 430: 2080-2095. PMID: 29782832, PMCID: PMC6003625, DOI: 10.1016/j.jmb.2018.05.025.Peer-Reviewed Original ResearchConceptsEssential DEAD-box proteinADP releaseDbp5's ATPase activityDEAD-box proteinsNucleotide exchange factorsDbp5 activityMRNA exportRNA metabolismExchange factorDbp5Cellular processesATPase cyclingNup159Gle1ATP affinityMechanochemical cycleATPase activityADPATP releaseDDX19NTPasesNucleoporinsDetailed characterizationRNARegulator
2017
Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells
Zhu S, Ding S, Wang P, Wei Z, Pan W, Palm NW, Yang Y, Yu H, Li HB, Wang G, Lei X, de Zoete MR, Zhao J, Zheng Y, Chen H, Zhao Y, Jurado KA, Feng N, Shan L, Kluger Y, Lu J, Abraham C, Fikrig E, Greenberg HB, Flavell RA. Nlrp9b inflammasome restricts rotavirus infection in intestinal epithelial cells. Nature 2017, 546: 667-670. PMID: 28636595, PMCID: PMC5787375, DOI: 10.1038/nature22967.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosis Regulatory ProteinsCARD Signaling Adaptor ProteinsCaspase 1DEAD-box RNA HelicasesEpithelial CellsFemaleImmunity, InnateInflammasomesInterleukin-18Intestinal MucosaIntestinesIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphate-Binding ProteinsPyroptosisReceptors, G-Protein-CoupledRNA, Double-StrandedRotavirusRotavirus Infections
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