2024
Covalent Polymer‐RNA Conjugates for Potent Activation of the RIG‐I Pathway
Palmer C, Pastora L, Kimmel B, Pagendarm H, Kwiatkowski A, Stone P, Arora K, Francini N, Fedorova O, Pyle A, Wilson J. Covalent Polymer‐RNA Conjugates for Potent Activation of the RIG‐I Pathway. Advanced Healthcare Materials 2024, e2303815. PMID: 38648653, PMCID: PMC11493851, DOI: 10.1002/adhm.202303815.Peer-Reviewed Original ResearchChemical design principlesActivation of RIG-I.Retinoic acid-inducible gene ICovalent conjugationRIG-I pathwayNuclease degradationThioether linkageRIG-I.Gene IRNA ligandsElectrostatic interactionsRIG-IDevelopment of therapeuticsPotent activityOligonucleotide therapeuticsNucleaseRNAAnalog carrierNanoparticlesDrug delivery barriersConjugatePolymeric carriersImmunostimulatory activityThioethersIn vivo delivery
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 featuresUS-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes
Zhang C, Shine M, Pyle AM, Zhang Y. US-align: universal structure alignments of proteins, nucleic acids, and macromolecular complexes. Nature Methods 2022, 19: 1109-1115. PMID: 36038728, DOI: 10.1038/s41592-022-01585-1.Peer-Reviewed Original ResearchConceptsStructure comparisonStructural biology studiesStructure alignmentDNA dockingMacromolecular complexesBiology studiesMultiple structure alignmentNucleic acidsDifferent moleculesRNAProteinFundamental importanceDNAComplex structureDockingUniversal protocolAlignmentExtensive optimizationFunctionComplexes
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 reportSignalingTranslationRoleTargetThe 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 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
Sequencing and Structure Probing of Long RNAs Using MarathonRT: A Next-Generation Reverse Transcriptase
Guo LT, Adams RL, Wan H, Huston NC, Potapova O, Olson S, Gallardo CM, Graveley BR, Torbett BE, Pyle AM. Sequencing and Structure Probing of Long RNAs Using MarathonRT: A Next-Generation Reverse Transcriptase. Journal Of Molecular Biology 2020, 432: 3338-3352. PMID: 32259542, PMCID: PMC7556701, DOI: 10.1016/j.jmb.2020.03.022.Peer-Reviewed Original ResearchConceptsLong RNA moleculesLong RNAsRNA moleculesRNA base modificationsGroup II intronsMutational profilingTranscriptome compositionRNA metabolismRNA researchBase modificationsPrimer extensionTool enzymeDiverse aspectsMixed populationEnzymeReverse transcriptionRNAStructural complexityReverse transcriptaseProfilingTranscriptase enzymeIntronsTranscription
2015
HOTAIR Forms an Intricate and Modular Secondary Structure
Somarowthu S, Legiewicz M, Chillón I, Marcia M, Liu F, Pyle AM. HOTAIR Forms an Intricate and Modular Secondary Structure. Molecular Cell 2015, 58: 353-361. PMID: 25866246, PMCID: PMC4406478, DOI: 10.1016/j.molcel.2015.03.006.Peer-Reviewed Original ResearchConceptsFunctional secondary structureFundamental cellular processesSecondary structureProtein-binding motifsProtein-binding domainsGroup II intronsMetastasis suppressor geneSecondary structure elementsCellular processesPhylogenetic analysisLncRNA moleculesEpidermal developmentChemical probingMolecular mechanismsSuppressor geneCancer progressionStructural organizationKey playersLncRNA HOTAIRHOTAIRStructure elementsRNAHomogenous formReceptor activatorIntrons
2014
The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain
Rawling DC, Kohlway AS, Luo D, Ding SC, Pyle AM. The RIG-I ATPase core has evolved a functional requirement for allosteric stabilization by the Pincer domain. Nucleic Acids Research 2014, 42: 11601-11611. PMID: 25217590, PMCID: PMC4191399, DOI: 10.1093/nar/gku817.Peer-Reviewed Original ResearchConceptsATPase coreRetinoic acid-inducible gene IAcid-inducible gene INon-self RNASeries of mutationsActivity of RIGMetazoan cellsHelicase coreAllosteric controlTerminal domainPattern recognition receptorsAlpha-helixBiophysical analysisGene IAllosteric stabilizationType I interferonEnzymatic activityRecognition receptorsViral RNAStructural studiesRNAI interferonAdjacent domainsDomainImportant role
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
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