2024
The West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles
Huston N, Tsao L, Brackney D, Pyle A. The West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2312080121. PMID: 38985757, PMCID: PMC11260092, DOI: 10.1073/pnas.2312080121.Peer-Reviewed Original ResearchConceptsWest Nile virus genomeWest Nile virusPositive-sense RNA virusesFunctional roleArthropod cell linesRiboregulatory elementsGenome foldingFlaviviral genomeRNA genomeIncreasing global threatVirus genomeGenomeRNA virusesStructural homologyHost-dependentSecondary structureLack of effective therapeuticsFunctional validationLocked nucleic acidStructural insightsRNA drugsCell linesArthropod-borneNucleic acidsAntisense locked nucleic acidNanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy
Wang-Bishop L, Wehbe M, Pastora L, Yang J, Kimmel B, Garland K, Becker K, Carson C, Roth E, Gibson-Corley K, Ulkoski D, Krishnamurthy V, Fedorova O, Richmond A, Pyle A, Wilson J. Nanoparticle Retinoic Acid-Inducible Gene I Agonist for Cancer Immunotherapy. ACS Nano 2024, 18: 11631-11643. PMID: 38652829, PMCID: PMC11080455, DOI: 10.1021/acsnano.3c06225.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsTumor microenvironmentLipid nanoparticlesBreast cancerResponse to ICIResponse to immune checkpoint inhibitorsInfiltration of CD8<sup>+</sup>Models of triple-negative breast cancerCD4<sup>+</sup> T cellsInhibition of tumor growthTriple-negative breast cancerRIG-IIonizable lipid nanoparticlesLung metastatic burdenIncrease tumor immunogenicityBreast tumor microenvironmentSignaling in vitroACTLA-4Immunogenic melanomaCheckpoint inhibitorsTumor immunogenicityImmunotherapeutic modalitiesCancer immunotherapyMetastatic burdenAPD-1
2021
Noncoding RNAs: biology and applications—a Keystone Symposia report
Cable J, Heard E, Hirose T, Prasanth KV, Chen L, Henninger JE, Quinodoz SA, Spector DL, Diermeier SD, Porman AM, Kumar D, Feinberg MW, Shen X, Unfried JP, Johnson R, Chen C, Wilusz JE, Lempradl A, McGeary SE, Wahba L, Pyle AM, Hargrove AE, Simon MD, Marcia M, Przanowska RK, Chang HY, Jaffrey SR, Contreras LM, Chen Q, Shi J, Mendell JT, He L, Song E, Rinn JL, Lalwani MK, Kalem MC, Chuong EB, Maquat LE, Liu X. Noncoding RNAs: biology and applications—a Keystone Symposia report. Annals Of The New York Academy Of Sciences 2021, 1506: 118-141. PMID: 34791665, PMCID: PMC9808899, DOI: 10.1111/nyas.14713.Peer-Reviewed Original ResearchConceptsPIWI-interacting RNAsKeystone Symposia reportPotential drug targetsRNA biologyHuman transcriptomeEpigenetic modificationsKeystone eSymposiumNoncoding RNAsCell signalingBasic biologyDrug targetsRNABiologyDisease mechanismsNucleotidesSpeciesTranscriptomeImportant roleRNAsTranscriptionSymposium reportSignalingTranslationRoleTargetInsights 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
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 virusCellsOverhangMoleculesSignalingIntratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses
Jiang X, Muthusamy V, Fedorova O, Kong Y, Kim DJ, Bosenberg M, Pyle AM, Iwasaki A. Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses. Journal Of Experimental Medicine 2019, 216: 2854-2868. PMID: 31601678, PMCID: PMC6888973, DOI: 10.1084/jem.20190801.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsAntineoplastic Agents, ImmunologicalCD8-Positive T-LymphocytesDose-Response Relationship, DrugGene Expression ProfilingImmunologic MemoryInjections, IntralesionalMaleMelanoma, ExperimentalMiceOligoribonucleotidesProgrammed Cell Death 1 ReceptorReceptors, Cell SurfaceTumor BurdenConceptsAntitumor responseNucleic acid-sensing pathwaysSignificant tumor growth delayNumber of CD8Systemic antitumor responseRobust antitumor responseAnti-PD1 antibodyB16 tumor growthImmunogenic tumor modelsCytosolic nucleic acid-sensing pathwaysSingle-agent treatmentTumor growth delayTumor metastasis modelNK cellsMetastasis modelT lymphocytesImmune responseExtended survivalIntratumoral deliveryImmune memoryMyeloid cellsTumor growthGrowth delayTumor microenvironmentTumor model
2013
Parts, assembly and operation of the RIG-I family of motors
Rawling DC, Pyle AM. Parts, assembly and operation of the RIG-I family of motors. Current Opinion In Structural Biology 2013, 25: 25-33. PMID: 24878341, PMCID: PMC4070197, DOI: 10.1016/j.sbi.2013.11.011.Peer-Reviewed Original Research
2005
Choosing between DNA and RNA: the polymer specificity of RNA helicase NPH-II
Kawaoka J, Pyle AM. Choosing between DNA and RNA: the polymer specificity of RNA helicase NPH-II. Nucleic Acids Research 2005, 33: 644-649. PMID: 15681616, PMCID: PMC548353, DOI: 10.1093/nar/gki208.Peer-Reviewed Original Research
2004
Prediction of functional tertiary interactions and intermolecular interfaces from primary sequence data
Pang PS, Jankowsky E, Wadley LM, Pyle AM. Prediction of functional tertiary interactions and intermolecular interfaces from primary sequence data. Journal Of Experimental Zoology Part B Molecular And Developmental Evolution 2004, 304B: 50-63. PMID: 15595717, DOI: 10.1002/jez.b.21024.Peer-Reviewed Original ResearchConceptsRNA-protein complexesPattern of conservationProtein-protein interactionsPrimary sequence dataRNA-proteinDifferent organismsSequence dataSequence informationIntermolecular interfaceEnergetic couplingTertiary interactionsMacromolecular interactionsRNAsGenesImportant intramolecular interactionsProteinSequenceIntramolecular interactionsRNAOrganismsSpeciesInteractionMutationsNumber of predictionsConservation
2002
mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties
Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM, Fisher PB. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 637-642. PMID: 11805321, PMCID: PMC117358, DOI: 10.1073/pnas.022637199.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAmino Acid SequenceAnimalsApoptosisCell DifferentiationCell DivisionCloning, MolecularDEAD-box RNA HelicasesDNA, ComplementaryGrowth InhibitorsHumansInterferon Type IInterferon-Induced Helicase, IFIH1MelanomaMolecular Sequence DataRecombinant ProteinsRNA HelicasesRNA, Double-StrandedSequence Homology, Amino AcidTumor Cells, CulturedTumor Stem Cell AssayConceptsRNA-dependent ATPase activityCaspase recruitment domainHelicase motifsHuman melanoma cellsRecruitment domainRNA helicase motifsRNA-dependent ATPaseMDA-5RNA helicase domainPutative RNA helicaseMelanoma cellsEarly response genesATPase activityProtein kinase C activationGrowth-suppressive propertiesMelanoma differentiation-associated gene 5Appropriate pharmacological manipulationKinase C activationHypothetical proteinsRNA helicaseHelicase domainDifferentiation-associated gene 5Mediator of IFNSubtraction hybridizationMda-5 expression
1994
Replacement of the conserved G.U with a G-C pair at the cleavage site of the Tetrahymena ribozyme decreases binding, reactivity, and fidelity.
Pyle AM, Moran S, Strobel SA, Chapman T, Turner DH, Cech TR. Replacement of the conserved G.U with a G-C pair at the cleavage site of the Tetrahymena ribozyme decreases binding, reactivity, and fidelity. Biochemistry 1994, 33: 13856-63. PMID: 7947794, DOI: 10.1021/bi00250a040.Peer-Reviewed Original Research
1992
RNA catalysis by a group I ribozyme. Developing a model for transition state stabilization.
Cech TR, Herschlag D, Piccirilli JA, Pyle AM. RNA catalysis by a group I ribozyme. Developing a model for transition state stabilization. Journal Of Biological Chemistry 1992, 267: 17479-17482. PMID: 1381347, DOI: 10.1016/s0021-9258(19)37064-4.Peer-Reviewed Original Research
1990
Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena.
Pyle AM, McSwiggen JA, Cech TR. Direct measurement of oligonucleotide substrate binding to wild-type and mutant ribozymes from Tetrahymena. Proceedings Of The National Academy Of Sciences Of The United States Of America 1990, 87: 8187-8191. PMID: 2236030, PMCID: PMC54920, DOI: 10.1073/pnas.87.21.8187.Peer-Reviewed Original ResearchConceptsSingle base changeBase-pairing interactionsGuanosine-binding siteRNA substratesSubstrate bindingRNA cleavageOligonucleotide substratesEfficient RNA cleavageTertiary interactionsBase changesRibozyme variantsTetrahymena ribozymeWeak substrateMutant ribozymesRibozymePolyacrylamide gelsEquilibrium dissociation constantsDeoxyribose sugarCatalytic activityDivalent cationsEnergetic stabilizationMutagenesisDissociation constantsTetrahymenaLow Mg2