2023
Structural insights into intron catalysis and dynamics during splicing
Xu L, Liu T, Chung K, Pyle A. Structural insights into intron catalysis and dynamics during splicing. Nature 2023, 624: 682-688. PMID: 37993708, PMCID: PMC10733145, DOI: 10.1038/s41586-023-06746-6.Peer-Reviewed Original Research
2022
A molecular beacon assay for monitoring RNA splicing
Omran QQ, Fedorova O, Liu T, Pyle AM. A molecular beacon assay for monitoring RNA splicing. Nucleic Acids Research 2022, 50: e74-e74. PMID: 35438748, PMCID: PMC9303364, DOI: 10.1093/nar/gkac242.Peer-Reviewed Original ResearchConceptsMolecular beaconsMolecular beacon assayHigher fluorescent signalHigh-throughput screening platformSmall moleculesAutocatalyzed reactionMolecular beacon approachKinetic characterizationReactionSmall molecule targetingInhibition constantsScreening platformSmall molecule inhibitorsFluorescent signalMolecule targetingMolecule inhibitorsMolecules
2021
Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi
Liu T, Pyle AM. Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi. Nucleic Acids Research 2021, 49: 12422-12432. PMID: 34850132, PMCID: PMC8643640, DOI: 10.1093/nar/gkab1077.Peer-Reviewed Original ResearchConceptsGroup II intronsSelf-splicing group II intronsPathogenic fungiDrug targetsAntifungal drug targetsSelf-splicing intronsHuman pathogenic fungiMitochondrial genomeNear-physiological conditionsPromising drug targetProtein cofactorsStriking diversitySequence dataIntronsFungal pathogensInformatics searchBioinformatics workflowsFungiDimorphic fungusStructural signaturesPathogensGenomeCofactorDiversityTarget
2020
Visualizing group II intron dynamics between the first and second steps of splicing
Manigrasso J, Chillón I, Genna V, Vidossich P, Somarowthu S, Pyle AM, De Vivo M, Marcia M. Visualizing group II intron dynamics between the first and second steps of splicing. Nature Communications 2020, 11: 2837. PMID: 32503992, PMCID: PMC7275048, DOI: 10.1038/s41467-020-16741-4.Peer-Reviewed Original ResearchConceptsGroup II intron splicingGroup II intronsSelf-splicing ribozymesGene-editing toolsIntron dynamicsEukaryotic spliceosomeActive site dynamicsIntron splicingRetrotransposable elementsCatalytic triadSplicingMolecular machinesConformational changesFirst residueMultiple conformationsSite dynamicsSpliceosomeIntronsStructural rearrangementsX-ray crystallographyEnzymatic assayStructural dataEnzymatic strategyFunctional dataActive site
2014
Principles of ion recognition in RNA: insights from the group II intron structures
Marcia M, Pyle AM. Principles of ion recognition in RNA: insights from the group II intron structures. RNA 2014, 20: 516-527. PMID: 24570483, PMCID: PMC3964913, DOI: 10.1261/rna.043414.113.Peer-Reviewed Original ResearchConceptsActive siteSite-bound ionsIon recognitionMetal ionsOrganic ionsLatter ionIon-binding sitesCatalytic ionsCrystal structureGU wobble pairsMonovalent ionsLarge RNA moleculesIonsStructural ionsBiophysical methodsGroup II intron structureGA mismatchesLong-range tertiary contactsRNA structureRNA foldingTertiary contactsWobble pairStructureCatalysisHeteronuclear
2003
Domains 2 and 3 Interact to Form Critical Elements of the Group II Intron Active Site
Fedorova O, Mitros T, Pyle AM. Domains 2 and 3 Interact to Form Critical Elements of the Group II Intron Active Site. Journal Of Molecular Biology 2003, 330: 197-209. PMID: 12823961, DOI: 10.1016/s0022-2836(03)00594-1.Peer-Reviewed Original ResearchA Group II Intron Inserted into a Bacterial Heat-Shock Operon Shows Autocatalytic Activity and Unusual Thermostability †
Adamidi C, Fedorova O, Pyle AM. A Group II Intron Inserted into a Bacterial Heat-Shock Operon Shows Autocatalytic Activity and Unusual Thermostability †. Biochemistry 2003, 42: 3409-3418. PMID: 12653544, DOI: 10.1021/bi027330b.Peer-Reviewed Original Research
2002
Group II introns: highly specific endonucleases with modular structures and diverse catalytic functions
Fedorova O, Su LJ, Pyle AM. Group II introns: highly specific endonucleases with modular structures and diverse catalytic functions. Methods 2002, 28: 323-335. PMID: 12431436, DOI: 10.1016/s1046-2023(02)00239-6.Peer-Reviewed Original ResearchProductive folding to the native state by a group II intron ribozyme11Edited by D. Draper
Swisher JF, Su LJ, Brenowitz M, Anderson VE, Pyle AM. Productive folding to the native state by a group II intron ribozyme11Edited by D. Draper. Journal Of Molecular Biology 2002, 315: 297-310. PMID: 11786013, DOI: 10.1006/jmbi.2001.5233.Peer-Reviewed Original Research
1998
More than one way to splice an RNA: branching without a bulge and splicing without branching in group II introns.
Chu VT, Liu Q, Podar M, Perlman PS, Pyle AM. More than one way to splice an RNA: branching without a bulge and splicing without branching in group II introns. RNA 1998, 4: 1186-202. PMID: 9769094, PMCID: PMC1369692, DOI: 10.1017/s1355838298980724.Peer-Reviewed Original Research
1995
Branch-point attack in group II introns is a highly reversible transesterification, providing a potential proofreading mechanism for 5'-splice site selection.
Chin K, Pyle AM. Branch-point attack in group II introns is a highly reversible transesterification, providing a potential proofreading mechanism for 5'-splice site selection. RNA 1995, 1: 391-406. PMID: 7493317, PMCID: PMC1482411.Peer-Reviewed Original ResearchConversion of a group II intron into a new multiple-turnover ribozyme that selectively cleaves oligonucleotides: elucidation of reaction mechanism and structure/function relationships.
Michels WJ, Pyle AM. Conversion of a group II intron into a new multiple-turnover ribozyme that selectively cleaves oligonucleotides: elucidation of reaction mechanism and structure/function relationships. Biochemistry 1995, 34: 2965-77. PMID: 7893710, DOI: 10.1021/bi00009a028.Peer-Reviewed Original Research
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 ResearchBuilding a kinetic framework for group II intron ribozyme activity: quantitation of interdomain binding and reaction rate.
Pyle AM, Green JB. Building a kinetic framework for group II intron ribozyme activity: quantitation of interdomain binding and reaction rate. Biochemistry 1994, 33: 2716-25. PMID: 8117737, DOI: 10.1021/bi00175a047.Peer-Reviewed Original ResearchConceptsGeneral base catalysisChemical stepLinear rangeMichaelis-Menten mechanismSplice-site hydrolysisMultiple-turnover kinetic analysesPH/rate profileEnergetic stabilizationBase catalysisActive siteGel filtration chromatographyRibozyme kineticsReaction rateFiltration chromatographySpecific hydrolysisKinetic frameworkKinetic analysisHydrolysisReactionLower Km valuesBase pairingRibozyme activityKcat
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