2024
Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions
Lee P, Sun Y, Soares A, Fai C, Picciotto M, Guo J. Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions. Molecular Cell 2024, 84: 3967-3978.e8. PMID: 39317199, PMCID: PMC11490368, DOI: 10.1016/j.molcel.2024.08.032.Peer-Reviewed Original ResearchTranslation initiation siteNeuronal pentraxin receptorAUG translational initiation siteAlternative translation initiation sitesN-terminal signal sequenceN-terminal transmembrane domainRNA secondary structureAlternative translation initiationN-terminal extensionTranslation initiationSignal sequenceProtein isoformsProtein localizationAUG initiatorTransmembrane domainWidespread mechanismSecondary structureInitiation siteAlternative usageAMPA-type glutamate receptorsProteoformsSecreted factorsProteinReduced AMPA receptorMRNA
2023
Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed −1 ribosomal frameshifting
Wei L, Sun Y, Guo J. Genome-wide CRISPR screens identify noncanonical translation factor eIF2A as an enhancer of SARS-CoV-2 programmed −1 ribosomal frameshifting. Cell Reports 2023, 42: 112987. PMID: 37581984, DOI: 10.1016/j.celrep.2023.112987.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Host factorsSARS-CoV-2 replicationSyndrome coronavirus 2SARS-CoV-2Eukaryotic translation initiation factor 2ACoronavirus 2Viral RNAGenome-wide CRISPR screenFactor 2APositive-strand RNA virusesGenome-wide CRISPRRNA virusesKnockout screensRNAInitiationStress promotes RNA G-quadruplex folding in human cells
Kharel P, Fay M, Manasova E, Anderson P, Kurkin A, Guo J, Ivanov P. Stress promotes RNA G-quadruplex folding in human cells. Nature Communications 2023, 14: 205. PMID: 36639366, PMCID: PMC9839774, DOI: 10.1038/s41467-023-35811-x.Peer-Reviewed Original ResearchConceptsHuman cellsMRNA stabilityCellular stress responseRG4 structuresG-quadruplex structuresRNA G4sDynamic regulationG-quadruplex foldingRich nucleic acidsStress responsePermissive conditionsRG4FoldingStress removalRegulatory impactNucleic acidsCellsDimethylsulfateRNAMotifGuanineMRNARegulationStressSequence
2022
Systematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregation
Isiktas A, Eshov A, Yang S, Guo J. Systematic generation and imaging of tandem repeats reveal base-pairing properties that promote RNA aggregation. Cell Reports Methods 2022, 2: 100334. PMID: 36452875, PMCID: PMC9701603, DOI: 10.1016/j.crmeth.2022.100334.Peer-Reviewed Original ResearchConceptsBase pairsRNA aggregationRNA-RNA interactionsLive-cell imagingConsecutive base pairsNoncanonical base pairsRNA aggregatesRepeat RNARepeat DNAMolecular basisRepeat sequencesMolecular mechanismsTandem repeatsRNAHexanucleotide repeatsStructural determinantsGGGGCC hexanucleotide repeatBase-pairing propertiesCommon pathological featureRepeatsSequenceUnifying modelGeneralizable approachDistinct propertiesEnhanced aggregationSecondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells
Lan TCT, Allan MF, Malsick LE, Woo JZ, Zhu C, Zhang F, Khandwala S, Nyeo SSY, Sun Y, Guo JU, Bathe M, Näär A, Griffiths A, Rouskin S. Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells. Nature Communications 2022, 13: 1128. PMID: 35236847, PMCID: PMC8891300, DOI: 10.1038/s41467-022-28603-2.Peer-Reviewed Original ResearchConceptsRNA genomeSARS-CoV-2 RNA genomeStructural ensemblesAlternative RNA conformationsSingle-nucleotide resolutionInfected cellsRNA biologyGenomic structureSARS-CoV-2 genomeCellular contextNucleotide resolutionFunctional characterizationGenomeRNA conformationEntire SARS-CoV-2 genomeProfiling studiesFull lengthRNAStimulation elementCellsBiologyBetacoronavirusesLittle experimental dataConformationPromotes
2021
Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting
Sun Y, Abriola L, Niederer RO, Pedersen SF, Alfajaro MM, Silva Monteiro V, Wilen CB, Ho YC, Gilbert WV, Surovtseva YV, Lindenbach BD, Guo JU. Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2023051118. PMID: 34185680, PMCID: PMC8256030, DOI: 10.1073/pnas.2023051118.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 replicationSARS-CoV-2Severe acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Vero E6 cellsHigh-throughput compound screenOpen reading frame 1bEffective antiviral strategiesCoronavirus 2E6 cellsAntiviral strategiesViral gene expressionCompound screenFluoroquinolone antibacterialsFrame 1bGene expressionRegulation of nonsense-mediated mRNA decay in neural development and disease
Lee PJ, Yang S, Sun Y, Guo JU. Regulation of nonsense-mediated mRNA decay in neural development and disease. Journal Of Molecular Cell Biology 2021, 13: 269-281. PMID: 33783512, PMCID: PMC8339359, DOI: 10.1093/jmcb/mjab022.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAberrant mRNAsNonsense-mediated mRNA decayMRNA decay functionCore NMD factorsMRNA surveillance mechanismGene regulation mechanismsQuality control mechanismsPremature termination codonNMD factorsPhysiological mRNAsOrganismal levelMRNA decayDevelopmental regulationGenetic evidenceMolecular basisTermination codonBiological functionsRegulation mechanismNeural developmentPhysiological functionsSurveillance mechanismNMDNeurodegenerative diseasesMRNACritical role
2020
C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression
Sun Y, Eshov A, Zhou J, Isiktas AU, Guo JU. C9orf72 arginine-rich dipeptide repeats inhibit UPF1-mediated RNA decay via translational repression. Nature Communications 2020, 11: 3354. PMID: 32620797, PMCID: PMC7335171, DOI: 10.1038/s41467-020-17129-0.Peer-Reviewed Original ResearchMeSH KeywordsAmyotrophic Lateral SclerosisAnimalsC9orf72 ProteinCell Line, TumorCell SurvivalDatasets as TopicDNA Repeat ExpansionEmbryo, MammalianFemaleFrontal LobeFrontotemporal DementiaHumansIntronsMiceNeuronsNonsense Mediated mRNA DecayPrimary Cell CultureProtein BiosynthesisRNA HelicasesRNA, MessengerRNA-SeqTrans-ActivatorsConceptsArginine-rich dipeptide repeatsNonsense-mediated decayRNA surveillanceTranslational repressionNMD inhibitionDipeptide repeatsRNA Decay mechanismsGlobal translational repressionStress granule formationC9ALS/FTDRNA decayFrameshift 1Repeat regionFamilial amyotrophic lateral sclerosisGranule formationCultured cellsFTD brainC9orf72 geneRepressionSurvival of neuronsRepeatsAmyotrophic lateral sclerosisMutantsGenesLateral sclerosisCoding functions of “noncoding” RNAs
Wei LH, Guo JU. Coding functions of “noncoding” RNAs. Science 2020, 367: 1074-1075. PMID: 32139529, DOI: 10.1126/science.aba6117.Commentaries, Editorials and LettersConceptsRNA regionsProtein-coding functionProtein-coding sequencesDistinct biological processesRNA sequencing studiesLong noncoding RNAPervasive transcriptionFunctional peptidesPervasive translationHuman genomeNoncoding RNAsTranslation eventsBiological processesSequencing studiesCell growthRNATranscriptomeGenomeTranscriptionLncRNAsPeptidesMicroproteinsTranslationSubsequent studiesRegion
2016
RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria
Guo J, Bartel D. RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria. Science 2016, 353: aaf5371-aaf5371. PMID: 27708011, PMCID: PMC5367264, DOI: 10.1126/science.aaf5371.Peer-Reviewed Original ResearchConceptsRNA G-quadruplexesEukaryotic cellsG-quadruplexStable four-stranded structuresG-quadruplexes in vitroG-quadruplex-forming sequencesPosttranscriptional gene regulationG-quadruplex-forming regionsFour-stranded structuresBacterial transcriptomesRNA regionsGene regulationEscherichia coliImpaired translationRNABacteriaCellsIn vitroEukaryotesTranscriptomeSequenceMachineryRegionRegulation
2015
Lin28A Binds Active Promoters and Recruits Tet1 to Regulate Gene Expression
Zeng Y, Yao B, Shin J, Lin L, Kim N, Song Q, Liu S, Su Y, Guo J, Huang L, Wan J, Wu H, Qian J, Cheng X, Zhu H, Ming G, Jin P, Song H. Lin28A Binds Active Promoters and Recruits Tet1 to Regulate Gene Expression. Molecular Cell 2015, 61: 153-160. PMID: 26711009, PMCID: PMC4779955, DOI: 10.1016/j.molcel.2015.11.020.Peer-Reviewed Original ResearchConceptsFunctions of Lin28ADNA sequences in vitroLet-7 miRNA biogenesisGenomic binding sitesTranscription start siteEmbryonic stem cells in vivoRNA-binding proteinsSequences in vitroRegulate gene expressionEpigenetic DNA modificationMRNA translation efficiencyDysregulated DNA methylationChIP-seqGenomic occupancyStart siteRNA-seqTranscriptional regulationTranslational efficiencyDNA methylationMiRNA biogenesisDNA modificationsMammalian systemsTarget genesTET1 knockdownGene expressionA septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation
Sun J, Bonaguidi M, Jun H, Guo J, Sun G, Will B, Yang Z, Jang M, Song H, Ming G, Christian K. A septo-temporal molecular gradient of sfrp3 in the dentate gyrus differentially regulates quiescent adult hippocampal neural stem cell activation. Molecular Brain 2015, 8: 52. PMID: 26337530, PMCID: PMC4559945, DOI: 10.1186/s13041-015-0143-9.Peer-Reviewed Original ResearchConceptsRadial glia-like neural stem cellsSepto-temporal axisAdult dentate gyrusDentate gyrusAdult hippocampal neurogenesisMouse dentate gyrusAdult mouse dentate gyrusHippocampal neurogenesisStem cell activityLevels of adult hippocampal neurogenesisIn situ hybridizationMechanisms regulating proliferationNeural stem cell activityQuantitative real-time PCRNeural stem cellsMCM2 expressionReal-time PCRCell activationMature neuronsPostnatal developmentSFRP3Stem cellsMolecular mechanismsProtein 3Suppressive activityTet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair
Yu H, Su Y, Shin J, Zhong C, Guo J, Weng Y, Gao F, Geschwind D, Coppola G, Ming G, Song H. Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nature Neuroscience 2015, 18: 836-843. PMID: 25915473, PMCID: PMC4446239, DOI: 10.1038/nn.4008.Peer-Reviewed Original Research
2014
Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the adult mouse brain
Guo J, Szulwach K, Su Y, Li Y, Yao B, Xu Z, Shin J, Xie B, Gao Y, Ming G, Jin P, Song H. Genome-wide antagonism between 5-hydroxymethylcytosine and DNA methylation in the adult mouse brain. Frontiers In Biology 2014, 9: 66-74. PMID: 25568643, PMCID: PMC4284063, DOI: 10.1007/s11515-014-1295-1.Peer-Reviewed Original ResearchActive DNA demethylationDNA methylomeDNA demethylationDNA methylationGenome-wide distribution of 5hmCGenome-wide distributionGenome-wide comparisonDistribution of 5hmCGranule neurons in vivoGene expression profilesGene bodiesCytosine modificationsNeuronal genomeMammalian nervous systemDNA modificationsGene expressionEmbryonic stem cellsDNAAdult mouse brainFunctional disparityGenesMethylomeCell typesIntegrated analysisGranule neuronsExpanded identification and characterization of mammalian circular RNAs
Guo J, Agarwal V, Guo H, Bartel D. Expanded identification and characterization of mammalian circular RNAs. Genome Biology 2014, 15: 409. PMID: 25070500, PMCID: PMC4165365, DOI: 10.1186/s13059-014-0409-z.Peer-Reviewed Original ResearchConceptsRNA-seq dataRNA-seqHuman circRNAsProtein-coding sequencesZinc-finger proteinProperties of circRNAsRegulate gene expressionCell type-specificCircular RNAsSequence conservationENCODE projectRibosome profilingMiRNA sitesTopological isoformsComputational pipelineBiological functionsMouse circRNAsGene expressionMiR-7 spongeLow abundanceCell typesExpression levelsRNACircRNAsSequence
2013
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain
Guo J, Su Y, Shin J, Shin J, Li H, Xie B, Zhong C, Hu S, Le T, Fan G, Zhu H, Chang Q, Gao Y, Ming G, Song H. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience 2013, 17: 215-222. PMID: 24362762, PMCID: PMC3970219, DOI: 10.1038/nn.3607.Peer-Reviewed Original ResearchConceptsCpH methylationNon-CpG cytosinesNon-CpG methylationSingle-base resolutionDNA methylome profilingDNA methyltransferase DNMT3ARepress transcriptionCpG dinucleotidesMethyltransferase DNMT3AProtein MeCP2DNANeuronal maturationMethylationMammalian brainDentate gyrus neuronsAdult mammalian brainCpGTranscriptionDinucleotideBisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter
Yeo M, Berglund K, Hanna M, Guo J, Kittur J, Torres M, Abramowitz J, Busciglio J, Gao Y, Birnbaumer L, Liedtke W. Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 4315-4320. PMID: 23440186, PMCID: PMC3600491, DOI: 10.1073/pnas.1300959110.Peer-Reviewed Original ResearchMeSH KeywordsAir Pollutants, OccupationalAnimalsBenzhydryl CompoundsCells, CulturedCentral Nervous System DiseasesCerebral CortexChloridesDNA-Binding ProteinsEpigenesis, GeneticFemaleHistone Deacetylase 1HumansK Cl- CotransportersMaleMiceNerve Tissue ProteinsNeuronsPhenolsRatsResponse ElementsSex CharacteristicsSymportersConceptsEffects of bisphenol AKcc2 promoterBisphenol A exposureKCC2 expressionCortical neuronsHistone deacetylase 1Binding of methyl-CpG-binding protein 2Potassium-chloride cotransporter 2KCC2 gene expressionMethyl-CpG-binding protein 2Knockdown of histone deacetylase 1Sexually dimorphic mannerSexually dimorphic effectsHuman neurodevelopmental disordersBisphenol-A effectsHuman cortical neuronsToxic mechanisms of bisphenol ANeuronal chlorideCotransporter 2Cortical slicesBinding protein 2KCC2Mouse damsDimorphic mannerInterneuron migrationSecreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis
Jang M, Bonaguidi M, Kitabatake Y, Sun J, Song J, Kang E, Jun H, Zhong C, Su Y, Guo J, Wang M, Sailor K, Kim J, Gao Y, Christian K, Ming G, Song H. Secreted Frizzled-Related Protein 3 Regulates Activity-Dependent Adult Hippocampal Neurogenesis. Cell Stem Cell 2013, 12: 215-223. PMID: 23395446, PMCID: PMC3569732, DOI: 10.1016/j.stem.2012.11.021.Peer-Reviewed Original ResearchConceptsNeural stem cellsAdult neurogenesisGranule neuronsStem cellsMature dentate granule neuronsDentate gyrus granule neuronsActivity-dependent regulationActivity-dependent mechanismsAdult mouse hippocampusDentate granule neuronsNeuronal circuit activityRegulates multiple phasesRadial neural stem cellsAdult neural stem cellsAdult hippocampal neurogenesisSecreted Wnt inhibitorNeural progenitor proliferationTonic inhibitionDendritic spine formationAcute releaseMature neuronsNeuronal maturationProgenitor proliferationWnt inhibitorsNeuronal activityChapter 3 Active DNA Demethylation and 5-Hydroxymethylcytosine
Guo J, Ming G, Song H. Chapter 3 Active DNA Demethylation and 5-Hydroxymethylcytosine. 2013, 69-83. DOI: 10.1016/b978-0-12-391494-1.00003-3.Peer-Reviewed Original ResearchActive DNA demethylationDNA demethylationRegulation of gene expression programsCytosine C5-methylationCharacterized epigenetic modificationDNA base 5-hydroxymethylcytosineGene expression programsEukaryotic cellsDNA methylationEpigenetic modificationsMammalian nervous systemDynamic regulationMolecular mechanismsExpression programsC5-methylationDemethylationDNANervous systemPathological conditionsCytosine
2012
Neuronal activation and insight into the plasticity of DNA methylation
Felling R, Guo J, Song H. Neuronal activation and insight into the plasticity of DNA methylation. Epigenomics 2012, 4: 125-127. PMID: 22449183, DOI: 10.2217/epi.12.2.Peer-Reviewed Original Research
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