Featured Publications
Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin
Machyna M, Kiefer L, Simon MD. Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin. Nature Structural & Molecular Biology 2020, 27: 297-304. PMID: 32157249, DOI: 10.1038/s41594-020-0390-z.Peer-Reviewed Original ResearchConceptsHybridization capture approachGenome-wide changesLong non-coding RNAsUnfolded protein responseNon-coding RNAsStrand exchange reactionLncRNA localizationIndividual RNAsRNA captureUncharacterized changesX chromosomeProtein responseHeat shockChromatinLncRNAsRNACapture approachBinding sitesNucleic acidsNucleotide chemistryRoX2AutosomesChromosomesRelocalizationSpeciesHigh-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M, Bowman SK, Kesner BA, Maier VK, Kingston RE, Lee JT. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 2013, 504: 465-469. PMID: 24162848, PMCID: PMC3904790, DOI: 10.1038/nature12719.Peer-Reviewed Original Research
2024
Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide
Moon M, Vock I, Streit A, Connor L, Senkina J, Ellman J, Simon M. Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide. ACS Chemical Biology 2024, 19: 2081-2086. PMID: 39192734, DOI: 10.1021/acschembio.4c00538.Peer-Reviewed Original ResearchCytochrome c oxidase 1Binding sitesRNA-small molecule interactionsPotential binding sitesTranscriptome-wide screeningSmall molecule disulfideSpinal muscular atrophyCellular RNARNA sitesTarget RNAMetabolic labelingSmall molecule bindingRNADisulfide analoguesLead moleculesMolecule bindingTranscriptomeFDA-approved drugsStructural probesMolecule interactionsCovalent attachmentDisulfide tetherThermodynamic propertiesTreat spinal muscular atrophyDisulfide
2022
Internally controlled RNA sequencing comparisons using nucleoside recoding chemistry
Courvan MCS, Niederer RO, Vock IW, Kiefer L, Gilbert WV, Simon MD. Internally controlled RNA sequencing comparisons using nucleoside recoding chemistry. Nucleic Acids Research 2022, 50: e110-e110. PMID: 36018791, PMCID: PMC9638901, DOI: 10.1093/nar/gkac693.Peer-Reviewed Original ResearchConceptsBiochemical manipulationRNA polymerase II inhibitionSodium arsenite stressSet of transcriptsNew biological understandingTranscript regulationArsenite stressMRNA associationRNA transcriptsBiological insightsHeat shockMetabolic labelBiological understandingRNA contentRNA levelsTranscriptsCell culturesII inhibitionBiological variationDDX5RibosomesMCM2RNAAbundanceRegulation
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 reportSignalingTranslationRoleTarget
2019
Reengineering a tRNA Methyltransferase To Covalently Capture New RNA Substrates
Smith TS, Zoltek MA, Simon MD. Reengineering a tRNA Methyltransferase To Covalently Capture New RNA Substrates. Journal Of The American Chemical Society 2019, 141: 17460-17465. PMID: 31626536, DOI: 10.1021/jacs.9b08529.Peer-Reviewed Original ResearchConceptsSubstrate specificityRNA substratesSubstrate RNARNA substrate specificityWild-type proteinCovalent RNA modificationsHigh-throughput sequencing assaysDouble mutantRNA modificationsTriple mutantSubstrate mutantsTRNA methyltransferaseProtein engineeringRNA transcriptsMutantsRational engineeringRNASubstrate screeningTRMASequencing assaysMethyltransferaseEnzymeProteinPowerful toolSpecificity
2018
Carbodiimide reagents for the chemical probing of RNA structure in cells
Wang PY, Sexton AN, Culligan WJ, Simon MD. Carbodiimide reagents for the chemical probing of RNA structure in cells. RNA 2018, 25: 135-146. PMID: 30389828, PMCID: PMC6298570, DOI: 10.1261/rna.067561.118.Peer-Reviewed Original ResearchConceptsConformation of RNAU nucleotidesIntact cellsChemical probesDimethyl sulfateNucleotides of RNASingle-stranded nucleotidesXist lncRNACellular contextNoncoding RNAsRNA elementsSHAPE reagentsAccessible nucleotidesRNA conformationRNA structureBiological contextChemical probingWatson-Crick faceCellular environmentFunctional roleCarbodiimide reagentRNA nucleotidesRNANucleotidesStructured regionsExpanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6‑Thioguanosine
Kiefer L, Schofield JA, Simon MD. Expanding the Nucleoside Recoding Toolkit: Revealing RNA Population Dynamics with 6‑Thioguanosine. Journal Of The American Chemical Society 2018, 140: 14567-14570. PMID: 30353734, PMCID: PMC6779120, DOI: 10.1021/jacs.8b08554.Peer-Reviewed Original Research
2017
Catching RNAs on chromatin using hybridization capture methods
Machyna M, Simon MD. Catching RNAs on chromatin using hybridization capture methods. Briefings In Functional Genomics 2017, 17: 96-103. PMID: 29126220, PMCID: PMC5888980, DOI: 10.1093/bfgp/elx038.Peer-Reviewed Original ResearchConceptsRNA affinity purificationHybridization capture methodsCross-linked chromatin extractsGenome-wide scaleEnrichment of RNAInteraction of lncRNAsLncRNA localizationChromatin isolationChromatin extractsSite of interactionCapture methodAffinity purificationBiological roleRNA targetsHybridization analysisRNARNA purificationChromatinLncRNAsOligonucleotide hybridizationPurificationDevelopment of methodsProteinCapture experimentsHybridization
2015
Probing Xist RNA Structure in Cells Using Targeted Structure-Seq
Fang R, Moss WN, Rutenberg-Schoenberg M, Simon MD. Probing Xist RNA Structure in Cells Using Targeted Structure-Seq. PLOS Genetics 2015, 11: e1005668. PMID: 26646615, PMCID: PMC4672913, DOI: 10.1371/journal.pgen.1005668.Peer-Reviewed Original ResearchConceptsStructure-seqRNA structureRNA conformationNon-coding RNA XISTLong non-coding RNA XISTX-chromosome inactivationSecondary structure mappingRNA of interestXist lncRNAMolecular evolutionC-repeatLncRNA functionsHigher-order structureXist functionRNA functionMammalian cellsMaster regulatorXISTSequencing readsChemical probingParallel sequencingTarget RNARNA XISTRNA basesRNATracking Distinct RNA Populations Using Efficient and Reversible Covalent Chemistry
Duffy EE, Rutenberg-Schoenberg M, Stark CD, Kitchen RR, Gerstein MB, Simon MD. Tracking Distinct RNA Populations Using Efficient and Reversible Covalent Chemistry. Molecular Cell 2015, 59: 858-866. PMID: 26340425, PMCID: PMC4560836, DOI: 10.1016/j.molcel.2015.07.023.Peer-Reviewed Original ResearchConceptsDynamic transcriptome analysisReversible covalent chemistryGlobal miRNA levelsMiRNA processing machineryTissue-specific transcriptionCovalent chemistryCultured human cellsChemical methodsImproved chemistryRNA turnoverRNA populationsTranscriptome analysisMethanethiosulfonate reagentsProcessing machineryHuman cellsHPDP-biotinHigh yieldsDisulfide bondsChemistryMiRNA levelsRNADifferent populationsTurnoverBondsReagents
2014
The Properties of Long Noncoding RNAs that Regulate Chromatin
Rutenberg-Schoenberg M, Sexton A, Simon M. The Properties of Long Noncoding RNAs that Regulate Chromatin. Annual Review Of Genomics And Human Genetics 2014, 17: 1-26. DOI: 10.1146/annurev-genom-090314-024939.Peer-Reviewed Original ResearchChromatin-based processesLong noncoding RNAMechanisms of lncRNAsChromatin biologyChromatin structureLncRNA functionsNuclear roleHuman lncRNAsPosttranscriptional regulationNoncoding RNAsRNA moleculesGene expressionFinal online publication dateBiochemical mechanismsBroader roleRNAUpstream roleLncRNAsOnline publication dateHuman physiologyChromatinGenomicsTranscriptionBiologyMechanism
2011
The genomic binding sites of a noncoding RNA
Simon MD, Wang CI, Kharchenko PV, West JA, Chapman BA, Alekseyenko AA, Borowsky ML, Kuroda MI, Kingston RE. The genomic binding sites of a noncoding RNA. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 20497-20502. PMID: 22143764, PMCID: PMC3251105, DOI: 10.1073/pnas.1113536108.Peer-Reviewed Original ResearchConceptsDosage compensationCross-linked chromatin extractsMale-specific lethal (MSL) complexLevel of chromatinSpecific genomic sitesImportant regulatory roleHybridization-based techniquesLethal complexLncRNAs bindWide mappingSites of proteinsGenomic sitesChromatin extractsGenomic targetsEndogenous RNAEndogenous lncRNARNA targetsProtein targetsRegulatory roleHybridization analysisRoX2RNAChromatinProteinBinds