2023
piRNA generation is associated with the pioneer round of translation in stem cells
Parambil S, Li D, Zelko M, Poulet A, van Wolfswinkel J. piRNA generation is associated with the pioneer round of translation in stem cells. Nucleic Acids Research 2023, 52: 2590-2608. PMID: 38142432, PMCID: PMC10954484, DOI: 10.1093/nar/gkad1212.Peer-Reviewed Original ResearchSMEDWI-1Pioneer roundStem cellsPlanarian stem cellsStem cell maintenanceStem cell stateNon-coding transcriptsPiRNA pathwayPIWI proteinsTransposon repressionBiogenesis pathwayPiRNA generationGenomic integritySmall RNAsCell maintenanceSuch transcriptsCell statesCytoplasmic poolTranscriptsCell coloniesCell healthPiRNAsDynamic poolTranscriptomeCellsFlavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism
Cohen J, Huang S, Koczwara K, Woods K, Ho V, Woodman K, Arbiser J, Daman K, Lek M, Emerson C, DeSimone A. Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism. Cell Death & Disease 2023, 14: 749. PMID: 37973788, PMCID: PMC10654915, DOI: 10.1038/s41419-023-06257-2.Peer-Reviewed Original ResearchConceptsMTOR-independent mechanismsFacioscapulohumeral muscular dystrophyDUX4 transcriptsDUX4 activityMultiple signal transduction pathwaysSignal transduction pathwaysTherapeutic developmentDUX4 proteinDUX4 expressionTransduction pathwaysPolyadenylation sitesChromosome 4DUX4 geneMechanisms of toxicityAutophagy pathwayExpression of ULK1DUX4Cellular autophagyCell deathRelevant pathwaysMuscular dystrophyMolecular methodsPathwaySkeletal muscleTranscriptsNormalizing need not be the norm: count-based math for analyzing single-cell data
Church S, Mah J, Wagner G, Dunn C. Normalizing need not be the norm: count-based math for analyzing single-cell data. Theory In Biosciences 2023, 143: 45-62. PMID: 37947999, DOI: 10.1007/s12064-023-00408-x.Peer-Reviewed Original ResearchDistinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages
Wilcox N, Yarovinsky T, Pandya P, Ramgolam V, Moro A, Wu Y, Nicoli S, Hirschi K, Bender J. Distinct hypoxia-induced translational profiles of embryonic and adult-derived macrophages. IScience 2023, 26: 107985. PMID: 38047075, PMCID: PMC10690575, DOI: 10.1016/j.isci.2023.107985.Peer-Reviewed Original ResearchBone marrow-derived macrophagesTranslation rateAffinity purification assaysGene expression programsTissue-resident macrophagesExpression programsTranscriptional signalsTranslational profilesTranscriptome analysisPosttranscriptional regulationMRNA translationRNA-seqMarrow-derived macrophagesPurification assaysRNA expression levelsProtein HuR.MRNA stabilityDistinct hypoxiaEmbryonic originPotential therapeutic targetTranscriptsExpression levelsAcute perturbationTherapeutic targetIschemic myocardiumMETTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells
Xiao Z, Wang S, Tian Y, Lv W, Sheng H, Zhan M, Huang Q, Zhang Z, Zhu L, Zhu C, Zhong H, Wen Q, Liu Z, Tan J, Xu Y, Yang M, Liu Y, Flavell R, Yang Q, Cao G, Yin Z. METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells. Cell Reports 2023, 42: 112684. PMID: 37355989, DOI: 10.1016/j.celrep.2023.112684.Peer-Reviewed Original ResearchConceptsM6A methylationMRNA stabilityΓδ T17 cellsEndogenous double-stranded RNADouble-stranded RNAActivation of STAT1MRNA metabolismMRNA turnoverGene expressionKey enzymeDsRNA contentT17 cellsMethylationFunctional specializationRNA contentΓδ TCritical roleMETTL3Numerous aspectsCellsT17Distinct subsetsM6ATranscriptsRNACochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Liu H, Liu H, Wang L, Song L, Jiang G, Lu Q, Yang T, Peng H, Cai R, Zhao X, Zhao T, Wu H. Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform. Nature Communications 2023, 14: 3085. PMID: 37248244, PMCID: PMC10227054, DOI: 10.1038/s41467-023-38621-3.Peer-Reviewed Original ResearchConceptsShort isoformEndocytic membrane retrievalRNA sequencing techniquesDiverse biological functionsInner hair cellsTranscript diversityUnannotated transcriptsRNA-seqAlternative isoformsMembrane retrievalBiological functionsGENCODE databasesKey proteinsIsoform resolutionSequencing techniquesSustained exocytosisIsoformsMechanistic understandingAuditory functionSanger sequencingHair cellsTranscriptsRT-PCRSynaptic transmissionAuditory phenotypeVisualizing gene expression changes in time, space, and single cells with expressyouRcell
Paganin M, Tebaldi T, Lauria F, Viero G. Visualizing gene expression changes in time, space, and single cells with expressyouRcell. IScience 2023, 26: 106853. PMID: 37250782, PMCID: PMC10220493, DOI: 10.1016/j.isci.2023.106853.Peer-Reviewed Original ResearchGene expressionSingle cellsGene expression variationBulk RNA sequencingGene expression changesProtein level changesHigh-throughput techniquesGene expression datasetsProteomic datasetsRNA sequencingExpression variationExpression changesExpression datasetsProtein levelsR packageCellsExpressionTranscriptsSequencingMassive advancementVariationComplex variations
2022
Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila
Bosch J, Ugur B, Pichardo-Casas I, Rabasco J, Escobedo F, Zuo Z, Brown B, Celniker S, Sinclair D, Bellen H, Perrimon N. Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila. ELife 2022, 11: e82709. PMID: 36346220, PMCID: PMC9681215, DOI: 10.7554/elife.82709.Peer-Reviewed Original ResearchConceptsSmall open reading framesClasses of genesShares sequence similarityOpen reading frameSequence similarityBicistronic transcriptBiological functionsPhenotypic analysisMitochondrial functionImportant regulatorThousands of peptidesNeuronal functionGenesWealth of informationTranscriptsAnimal lethalityPeptidesRecent studiesParalogsDrosophilaSmORFsMitochondriaRegulatorRegulatesNeuronal peptidesInternally 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 variationDDX5RibosomesMCM2RNAAbundanceRegulationInvestigating Sources of Zeros in 10× Single-Cell RNAseq Data
Slowik H, Zyla J, Marczyk M. Investigating Sources of Zeros in 10× Single-Cell RNAseq Data. Lecture Notes In Computer Science 2022, 13347: 71-80. DOI: 10.1007/978-3-031-07802-6_6.Peer-Reviewed Original ResearchSingle-cell levelSingle-cell RNA sequencingSingle-cell RNAseq dataNumber of transcriptsMulti-omics dataGene expression estimatesRibosomal genesRNA sequencingExpression profilingEnrichment analysisRNAseq dataBiological pathwaysSequencing platformsExpression dataGenesExpression estimatesIndividual cellsBreast cancer cell linesCancer cell linesCell linesSingle experimentLow mappabilityTranscriptsSequencingProfilingMeasuring mRNA Decay with Roadblock‐qPCR
Watson MJ, Thoreen CC. Measuring mRNA Decay with Roadblock‐qPCR. Current Protocols 2022, 2: e344. PMID: 35041257, PMCID: PMC8830782, DOI: 10.1002/cpz1.344.Peer-Reviewed Original ResearchConceptsMRNA stabilityPost-transcriptional regulatory stepsPre-existing mRNAsMRNA decay kineticsQuantitative PCRN-ethylmaleimideGene functionGene regulationGeneral transcriptionNascent mRNARegulatory stepEndogenous mRNACDNA poolsGene expressionLiving cellsTranscriptionCell functionMRNAReverse transcriptionCDNA synthesisMRNA levelsCellsTranscriptsRNACommon strategy
2021
OncoSplicing: an updated database for clinically relevant alternative splicing in 33 human cancers
Zhang Y, Yao X, Zhou H, Wu X, Tian J, Zeng J, Yan L, Duan C, Liu H, Li H, Chen K, Hu Z, Ye Z, Xu H. OncoSplicing: an updated database for clinically relevant alternative splicing in 33 human cancers. Nucleic Acids Research 2021, 50: d1340-d1347. PMID: 34554251, PMCID: PMC8728274, DOI: 10.1093/nar/gkab851.Peer-Reviewed Original ResearchConceptsAlternative splicingCancer-specific splicing eventsDifferential alternative splicingHuman cancersTCGA tumor samplesSplicing differencesSplicing eventsProtein complexityAdjacent normal samplesSplicingGene expressionSplicing dataNormal samplesAbnormal splicingIntegrative viewMRNA levelsDifferential analysisTumor samplesTranscriptsInterrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH
Savulescu A, Brackin R, Bouilhol E, Dartigues B, Warrell J, Pimentel M, Beaume N, Fortunato I, Dallongeville S, Boulle M, Soueidan H, Agou F, Schmoranzer J, Olivo-Marin J, Franco C, Gomes E, Nikolski M, Mhlanga M. Interrogating RNA and protein spatial subcellular distribution in smFISH data with DypFISH. Cell Reports Methods 2021, 1: 100068. PMID: 35474672, PMCID: PMC9017151, DOI: 10.1016/j.crmeth.2021.100068.Peer-Reviewed Original ResearchConceptsSubcellular localizationSingle-molecule RNA fluorescenceSingle-cell RNA sequencingNumber of transcriptsSmFISH dataRNA fluorescenceRNA sequencingHybridization dataBiological insightsLocalization patternsSubcellular distributionPatterns of clusteringCellular architectureRNACellular subtypesSkeletal muscle fibersCell micropatterningProtein immunolabelingPhysiological systemsCellsLocalizationBasis of quantificationSpatial distributionTranscriptsSequencingSTL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts
Zimmer JT, Rosa-Mercado NA, Canzio D, Steitz JA, Simon MD. STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts. Molecular Cell 2021, 81: 4398-4412.e7. PMID: 34520723, PMCID: PMC9020433, DOI: 10.1016/j.molcel.2021.08.019.Peer-Reviewed Original ResearchConceptsPause releaseRNA polymerase II transcriptsRNA polymerase II moleculesCis-acting DNA elementsTATA box-containing promotersPolymerase II transcriptsPromoter-proximal pausingCritical regulatory functionsTranscriptional regulationRNA turnoverTranscriptional controlDNA elementsTranscriptional shutdownPause sitesHyperosmotic stressRegulatory mechanismsRegulatory functionsPrinciples of regulationHormonal stimuliPausingPremature terminationTranscriptsRegulationWho let the DoGs out? – biogenesis of stress-induced readthrough transcripts
Rosa-Mercado NA, Steitz JA. Who let the DoGs out? – biogenesis of stress-induced readthrough transcripts. Trends In Biochemical Sciences 2021, 47: 206-217. PMID: 34489151, PMCID: PMC8840951, DOI: 10.1016/j.tibs.2021.08.003.Peer-Reviewed Original ResearchConceptsCellular stress responseHuman protein-coding genesStress responseProtein-coding genesDoG inductionNascent mRNAReadthrough transcriptionTranscriptional landscapeDifferent stress conditionsReadthrough transcriptsStress conditionsViral proteinsBiogenesisStress removalGenesTranscriptsCell exposureProduction playTranscriptionRNAProteinMRNAHostProductionHallmarkDirect characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH
Reilly SK, Gosai SJ, Gutierrez A, Mackay-Smith A, Ulirsch JC, Kanai M, Mouri K, Berenzy D, Kales S, Butler GM, Gladden-Young A, Bhuiyan RM, Stitzel ML, Finucane HK, Sabeti PC, Tewhey R. Direct characterization of cis-regulatory elements and functional dissection of complex genetic associations using HCR–FlowFISH. Nature Genetics 2021, 53: 1166-1176. PMID: 34326544, PMCID: PMC8925018, DOI: 10.1038/s41588-021-00900-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingBayes TheoremClustered Regularly Interspaced Short Palindromic RepeatsDelta-5 Fatty Acid DesaturaseDeoxyribonuclease IFatty Acid DesaturasesFlow CytometryGATA1 Transcription FactorHumansIn Situ Hybridization, FluorescenceK562 CellsLIM Domain ProteinsModels, GeneticPolymorphism, Single NucleotideProto-Oncogene ProteinsQuantitative Trait LociRegulatory Sequences, Nucleic AcidRNA, Guide, CRISPR-Cas SystemsConceptsCis-regulatory elementsGenome-wide association signalsGenome functionEpigenetic mappingComplex genetic associationsFunctional dissectionNearest geneGenetic variationAssociation signalsNative transcriptsTarget genesCausal variantsMultiple genesEndogenous functionsReporter assaysGenesCre activitySitu hybridizationGenetic associationFlow cytometryLociTranscriptsHierarchical Bayesian modelReaction fluorescenceHybridization
2020
Transcriptomic organization of the human brain in post-traumatic stress disorder
Girgenti MJ, Wang J, Ji D, Cruz DA, Stein M, Gelernter J, Young K, Huber B, Williamson D, Friedman M, Krystal J, Zhao H, Duman R. Transcriptomic organization of the human brain in post-traumatic stress disorder. Nature Neuroscience 2020, 24: 24-33. PMID: 33349712, DOI: 10.1038/s41593-020-00748-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutopsyBrain ChemistryCohort StudiesDepressive Disorder, MajorFemaleGene Expression RegulationGene Regulatory NetworksGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInterneuronsMaleMiddle AgedNerve Tissue ProteinsSex CharacteristicsStress Disorders, Post-TraumaticTranscriptomeYoung AdultConceptsGenome-wide association studiesSignificant gene networksDifferential gene expressionSystems-level evidenceSignificant genetic liabilityMajor depressive disorder cohortGene networksTranscriptomic organizationTranscriptomic landscapeDownregulated setsGenomic networksGene expressionAssociation studiesMolecular determinantsExtensive remodelingGenotype dataSexual dimorphismSignificant divergenceMolecular profileNetwork analysisELFN1TranscriptsDimorphismPostmortem tissueDivergenceThe NBDY Microprotein Regulates Cellular RNA Decapping
Na Z, Luo Y, Schofield JA, Smelyansky S, Khitun A, Muthukumar S, Valkov E, Simon MD, Slavoff SA. The NBDY Microprotein Regulates Cellular RNA Decapping. Biochemistry 2020, 59: 4131-4142. PMID: 33059440, PMCID: PMC7682656, DOI: 10.1021/acs.biochem.0c00672.Peer-Reviewed Original ResearchConceptsP-bodiesNonsense-mediated decay factorsKO cellsSmall open reading framesCytoplasmic ribonucleoprotein granulesOpen reading frameSubstrate transcriptsCellular transcriptomeRibonucleoprotein granulesTarget transcriptsRNA stabilityKnockout cellsUTR lengthReading frameGlobal profilingProteogenomic identificationMacromolecular complexesHuman RNACellular RNACytoplasmic RNAGene stabilityAmino acidsCell growthMicroproteinsTranscriptsModulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo
Hoppe C, Bowles JR, Minchington TG, Sutcliffe C, Upadhyai P, Rattray M, Ashe HL. Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo. Developmental Cell 2020, 54: 727-741.e7. PMID: 32758422, PMCID: PMC7527239, DOI: 10.1016/j.devcel.2020.07.007.Peer-Reviewed Original ResearchConceptsDrosophila embryosCell fate decisionsMorphogen gradient interpretationTarget gene transcriptsSingle-cell resolutionBMP gradientMRNA outputAxis patterningCell fateExpression domainsTranscriptional responsePromoter sequencesGene transcriptsProtein gradientGradient interpretationBurst kineticsBMPEmbryosEnhancerClassic exampleCellsActivation rateMorphogensTranscriptsGeneral featuresGlobal Profiling of Cellular Substrates of Human Dcp2
Luo Y, Schofield J, Simon MD, Slavoff SA. Global Profiling of Cellular Substrates of Human Dcp2. Biochemistry 2020, 59: 4176-4188. PMID: 32365300, PMCID: PMC7641959, DOI: 10.1021/acs.biochem.0c00069.Peer-Reviewed Original ResearchConceptsDecapping enzymeFirst committed stepCellular transcriptsP-bodiesRNA decayCommitted stepHuman transcriptomeMammalian cellsMolecular marksKnockout cellsGlobal profilingConsensus sequenceCellular substratesDCP2Human cellsTranscriptsEnzymeEnzyme substrateCellsDistinct subsetsTranscriptomeAdditive effectEnrichmentRNACytoplasm
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