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 acid
2022
The 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 ResearchConceptsRNA 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 features
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 ResearchConceptsRIG-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 featuresReceptorsComprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms
Huston NC, Wan H, Strine MS, de Cesaris Araujo Tavares R, Wilen CB, Pyle AM. Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms. Molecular Cell 2021, 81: 584-598.e5. PMID: 33444546, PMCID: PMC7775661, DOI: 10.1016/j.molcel.2020.12.041.Peer-Reviewed Original ResearchConceptsRNA structureSecondary structureRNA virusesSARS-CoV-2 RNA genomeNovel regulatory motifsSingle-nucleotide resolutionDownstream functional analysisRNA drug targetsPositive-sense RNA virusesGenome architectureGenomic structureEvolutionary analysisRegulatory motifsSARS-CoV-2 genomeViral life cycleRNA genomeFunctional analysisGenomeDrug targetsPrimer designInfected cellsViral RNADepth structural analysisLife cycleΒ-coronavirus
2020
The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome
de Cesaris Araujo Tavares R, Mahadeshwar G, Wan H, Huston NC, Pyle AM. The Global and Local Distribution of RNA Structure throughout the SARS-CoV-2 Genome. Journal Of Virology 2020, 95: 10.1128/jvi.02190-20. PMID: 33268519, PMCID: PMC8092842, DOI: 10.1128/jvi.02190-20.Peer-Reviewed Original ResearchSARS-CoV-2 genomeRNA structureRNA genomeRNA virusesViral genomeIndividual RNA structuresDrug targetsSARS-CoV-2 RNA genomeSilico pipelineMost RNA virusesRNA structural featuresComplex viral genomesRNA drug targetsStructured viral RNAsPotential drug targetsViral RNAViral infection cycleBase pair contentRNA biologyStructural ORFsLong genomeCellular mixturesGenomeRNA transcriptsInfection cycleSmall-Molecule Antagonists of the RIG‑I Innate Immune Receptor
Rawling DC, Jagdmann GE, Potapova O, Pyle AM. Small-Molecule Antagonists of the RIG‑I Innate Immune Receptor. ACS Chemical Biology 2020, 15: 311-317. PMID: 31944652, DOI: 10.1021/acschembio.9b00810.Peer-Reviewed Original ResearchConceptsInnate immune systemRIG-I receptorRole of RIGSmall molecule antagonistsPotent RIGAutoimmune disordersAntimicrobial therapyRange of diseasesImmune systemInterferon responseVertebrate innate immune systemImmune receptorsReceptorsNew drug design strategiesAntagonistRNA virusesDrug design strategiesCOPD
2013
Defining the functional determinants for RNA surveillance by RIG‐I
Kohlway A, Luo D, Rawling DC, Ding SC, Pyle AM. Defining the functional determinants for RNA surveillance by RIG‐I. EMBO Reports 2013, 14: 772-779. PMID: 23897087, PMCID: PMC3790051, DOI: 10.1038/embor.2013.108.Peer-Reviewed Original ResearchConceptsMelanoma differentiation-associated gene 5Robust ATPase activityDuplex RNA substrateMinimal functional unitATPase activityRetinoic acid-inducible geneInnate immune machineryAcid-inducible geneRNA surveillanceDifferentiation-associated gene 5RNA substratesIntracellular RNA sensorsDuplex RNARNA complexRNA targetsGene 5RNA virusesDistinct conformationsRNA sensorsDsRNA complexImmune machineryRNA duplexesInterferon responseFunctional determinantsFunctional units
2002
The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding
Pang PS, Jankowsky E, Planet PJ, Pyle AM. The hepatitis C viral NS3 protein is a processive DNA helicase with cofactor enhanced RNA unwinding. The EMBO Journal 2002, 21: 1168-1176. PMID: 11867545, PMCID: PMC125889, DOI: 10.1093/emboj/21.5.1168.Peer-Reviewed Original ResearchConceptsRNA unwindingHelicase activityDNA helicase activityCytoplasmic RNA virusesProcessive DNA helicaseImportant drug targetsReplicative DNA intermediatesNS3 helicase activityViral NS3 proteinDNA helicaseDuplex unwindingPhylogenetic analysisReplicative roleProcessive helicaseDNA intermediatesHelicaseHost DNARNA virusesRNA activityRNA replicationDrug targetsNS3 proteinUnwindingCentral roleDNA