2021
Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA
Ren X, Gelinas AD, Linehan M, Iwasaki A, Wang W, Janjic N, Pyle A. Evolving A RIG-I Antagonist: A Modified DNA Aptamer Mimics Viral RNA. Journal Of Molecular Biology 2021, 433: 167227. PMID: 34487794, DOI: 10.1016/j.jmb.2021.167227.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, ViralAptamers, NucleotideBinding SitesCloning, MolecularCrystallography, X-RayDEAD Box Protein 58Escherichia coliGene ExpressionGenetic VectorsHumansImmunologic FactorsKineticsModels, MolecularMolecular MimicryMutationNucleic Acid ConformationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsReceptors, ImmunologicRecombinant ProteinsRNA, ViralSELEX Aptamer TechniqueConceptsHigh-resolution crystal structuresResolution crystal structureRIG-I receptorResult of mutationsSame amino acidsVertebrate organismsProtein receptorsInnate immune receptorsRNA virusesImmune receptorsAmino acidsTool compoundsViral ligandsViral RNAImportant receptorPathogenic moleculesGeneralizable strategyDNA aptamersMolecular mimicryCentral roleDisease statesReceptorsTerminusRNAOrganisms
2019
RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Recognition of RNA Targets: The Influence of Terminal Base Pair Sequence and Overhangs on Affinity and Signaling. Cell Reports 2019, 29: 3807-3815.e3. PMID: 31851914, DOI: 10.1016/j.celrep.2019.11.052.Peer-Reviewed Original ResearchConceptsRNA moleculesRIG-I activationBase pair sequenceHost RNA moleculesViral RNA moleculesRIG-I recognitionMolecular basisRNA variantsRNA targetsPair sequenceHuman cellsBase pairsImmune receptorsMechanisms of evasionTerminal base pairsLigand affinityWhole animalInterferon responseDeadly pathogenRNA therapeuticsMarburg virusCellsOverhangMoleculesSignalingRIG-I Selectively Discriminates against 5′-Monophosphate RNA
Ren X, Linehan MM, Iwasaki A, Pyle AM. RIG-I Selectively Discriminates against 5′-Monophosphate RNA. Cell Reports 2019, 26: 2019-2027.e4. PMID: 30784585, DOI: 10.1016/j.celrep.2019.01.107.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesDEAD Box Protein 58HEK293 CellsHumansMiceMice, Inbred C57BLMolecular Dynamics SimulationProtein BindingRNA, Viral
2018
A minimal RNA ligand for potent RIG-I activation in living mice
Linehan MM, Dickey TH, Molinari ES, Fitzgerald ME, Potapova O, Iwasaki A, Pyle AM. A minimal RNA ligand for potent RIG-I activation in living mice. Science Advances 2018, 4: e1701854. PMID: 29492454, PMCID: PMC5821489, DOI: 10.1126/sciadv.1701854.Peer-Reviewed Original ResearchConceptsStem-loop RNAInterferon-stimulated genesImmune systemPotent synthetic activatorVertebrate immune systemType I interferonInnate immune systemRIG-I receptorRIG-I activationExpression networksRemodeling factorsPotent RIGRNA sequencingSpecific genesRNA ligandsI interferonAntiviral defenseInterferon responseRNA sensorsPolycytidylic acidSynthetic activatorsMiceInterferonGenesRNA
2017
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingDEAD Box Protein 58FemaleHumansImmunity, InnateInterferonsMaleMonocytesReceptors, ImmunologicSignal TransductionConceptsType I IFNsI IFNsI interferonOlder adultsIFN inductionRetinoic acid-inducible gene IAcid-inducible gene IHealthy human donorsType I interferonRespiratory influenzaProinflammatory cytokinesVirus infectionType I IFN genesAdult monocytesAntiviral resistanceTranscription factor IRF8IFN responseHuman donorsMonocytesIncreased proteasomal degradationHuman monocytesYoung adultsIRF8 expressionIAV RNAInfected cellsSensing Self and Foreign Circular RNAs by Intron Identity
Chen YG, Kim MV, Chen X, Batista PJ, Aoyama S, Wilusz JE, Iwasaki A, Chang HY. Sensing Self and Foreign Circular RNAs by Intron Identity. Molecular Cell 2017, 67: 228-238.e5. PMID: 28625551, PMCID: PMC5610545, DOI: 10.1016/j.molcel.2017.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceDEAD Box Protein 58Encephalitis Virus, Venezuelan EquineEncephalomyelitis, Venezuelan EquineHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmune ToleranceImmunity, InnateIntronsMiceNucleic Acid ConformationProtein BindingRAW 264.7 CellsReceptors, ImmunologicRNARNA Processing, Post-TranscriptionalRNA-Binding ProteinsRNA, CircularRNA, MessengerSpliceosomesTransfectionConceptsCircular RNAsInnate immunity genesMammalian transcriptionDiverse RNACytoplasmic fociHuman circRNAsMammalian cellsImmunity genesEndogenous splicingHuman intronsInnate immune sensingPrimary sequenceCircRNA sequenceRNA structureCircRNAsUnknown functionIntronsRNASensor RIGImmune sensingInnate immunitySelf-nonself discriminationPotent inductionSequenceBiogenesis
2013
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13910-13915. PMID: 23918369, PMCID: PMC3752242, DOI: 10.1073/pnas.1303275110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesFlow CytometryHistological TechniquesImmunity, InnateImmunohistochemistryInfluenza A virusMembrane GlycoproteinsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRespiratory Tract InfectionsSignal TransductionToll-Like Receptor 7Viral LoadVirus ReplicationConceptsToll-like receptor 7Innate immune responseRespiratory tractInfected wild-type miceHost innate immune responseAirways of miceViral target cellsWild-type miceAcid-inducible gene 1RIG-I pathwayPattern recognition receptorsHost innate defenseViral replication efficiencyInflammatory mediatorsBronchoalveolar lavageViral loadProinflammatory programProinflammatory responseReceptor 7IAV infectionInflammatory responseVirus infectionLow doseViral replicationVirus replication
2009
Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 2770-2775. PMID: 19196953, PMCID: PMC2650341, DOI: 10.1073/pnas.0807694106.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyAutophagy-Related Protein 5Cells, CulturedDEAD Box Protein 58DEAD-box RNA HelicasesDNA, MitochondrialEnzyme-Linked Immunosorbent AssayFlow CytometryInterferon Type IMacrophagesMiceMicrotubule-Associated ProteinsMitochondriaReactive Oxygen SpeciesReverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsReactive oxygen speciesDysfunctional mitochondriaInnate antiviral defenseAntiviral defenseKey antiviral cytokinesAbsence of autophagyMitochondrial reactive oxygen speciesHomeostatic regulationRole of autophagyTreatment of cellsIPS-1RLR signalingVesicular stomatitis virusAutophagy resultsRNA virusesWT cellsMitochondriaAutophagyType I IFNStomatitis virusRLRLike receptorsOxygen speciesNeurodegenerative diseasesInflammatory disorders