2024
Proteolethargy is a pathogenic mechanism in chronic disease
Dall'Agnese A, Zheng M, Moreno S, Platt J, Hoang A, Kannan D, Dall'Agnese G, Overholt K, Sagi I, Hannett N, Erb H, Corradin O, Chakraborty A, Lee T, Young R. Proteolethargy is a pathogenic mechanism in chronic disease. Cell 2024 PMID: 39610243, DOI: 10.1016/j.cell.2024.10.051.Peer-Reviewed Original ResearchPathogenic signalsExcessive reactive oxygen speciesMobility phenotypeCellular functionsAffected proteinsPathogenic mechanismsReactive oxygen speciesCysteine residuesSpectra of proteinsProtein mobilityPathogenic stimuliPathogenic featuresOxygen speciesMolecular levelCellular mechanismsDiverse chronic diseasesProteinChronic diseasesAn RNA-centric view of transcription and genome organization
Henninger J, Young R. An RNA-centric view of transcription and genome organization. Molecular Cell 2024, 84: 3627-3643. PMID: 39366351, PMCID: PMC11495847, DOI: 10.1016/j.molcel.2024.08.021.Peer-Reviewed Original ResearchConceptsGene regulationGenome architectureTranscriptional regulationModel of transcriptional regulationAssembly of protein complexesAssembly of transcription complexesLocal genome architectureSilencing of genesGenomic compartmentsGenome organizationGenomic structureRNA polymeraseChromatin regulationTranscription complexActive genesProtein complexesRNA moleculesTranscription factorsGenomeProtein kinaseSpecific genesGenesFeedback regulationRNASpatial compartmentsRNA and condensates: Disease implications and therapeutic opportunities
Han T, Portz B, Young R, Boija A, Klein I. RNA and condensates: Disease implications and therapeutic opportunities. Cell Chemical Biology 2024, 31: 1593-1609. PMID: 39303698, DOI: 10.1016/j.chembiol.2024.08.009.Peer-Reviewed Original ResearchConceptsRegulate key cellular processesDiverse RNA speciesRNA speciesTarget RNACompartmentalizing proteinsCellular processesRNA moleculesMembraneless organellesRNA roleBiomolecular condensatesRNA-based therapiesComplex diseasesRNA abnormalitiesRNADisease pathogenesisCondensate formationProperties of condensatesTherapeutic strategiesSmall moleculesOrganellesMislocalizationOverexpressionProteinSpeciesNeurological disordersMECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons
Liu Y, Flamier A, Bell G, Diao A, Whitfield T, Wang H, Wu Y, Schulte F, Friesen M, Guo R, Mitalipova M, Liu X, Vos S, Young R, Jaenisch R. MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons. Neuron 2024, 112: 1943-1958.e10. PMID: 38697112, DOI: 10.1016/j.neuron.2024.04.007.Peer-Reviewed Original ResearchPromoter-proximal regionRNA polymerase IIPolymerase IIHuman neuronsMethylated DNA binding protein MeCP2RNA Pol IIWild-typeLoss of gene activityAutism risk genesPol IIPositive cofactorCpG islandsTranscriptional regulationModulate transcriptionProtein MeCP2Patient mutationsNeurodevelopmental disorder Rett syndromeGene activationRisk genesProteomic analysisNeuronal genesRett syndromeGene expressionGenesRNA
2023
TIF1γ Counteracts Ferroptosis to Drive Erythroid Progenitor Differentiation
Rossmann M, Yang S, Abraham B, Wang Y, Young R, Hekimi S, Zon L. TIF1γ Counteracts Ferroptosis to Drive Erythroid Progenitor Differentiation. Blood 2023, 142: 8. DOI: 10.1182/blood-2023-184853.Peer-Reviewed Original ResearchTranscription elongationErythroid differentiationErythroid lineageNucleotide metabolismHematopoietic stem cell differentiationCell fate decisionsGenome-wide expressionChromatin immunoprecipitation analysisOnset of hematopoiesisTranscription regulatory processesErythroid progenitor differentiationStem cell differentiationElectron transport chainInhibitor of ferroptosisTranscriptional intermediary factor 1 gammaEnzyme dihydroorotate dehydrogenaseChromatin factorsSuppressor screenMutant embryosFate decisionsTranscriptome profilingZebrafish embryosProgenitor differentiationLineage differentiationBlood differentiation
1990
Conditional Mutations Occur Predominantly in Highly Conserved Residues of RNA Polymerase II Subunits
Scafe C, Martin C, Nonet M, Podos S, Okamura S, Young R. Conditional Mutations Occur Predominantly in Highly Conserved Residues of RNA Polymerase II Subunits. Molecular And Cellular Biology 1990, 10: 1270-1275. DOI: 10.1128/mcb.10.3.1270-1275.1990.Peer-Reviewed Original ResearchRNA polymerase II largest subunitRNA polymerase mutantsAmino acid residuesRPB1 geneLarge subunitInvariant residuesEucaryotic organismsPolymerase mutantsConditional mutationsYeast cellsSequence analysisAcid residuesRPB2RPB1MutationsCold sensitivityResiduesYeastMutantsCellsHomologyPlasmidGenesRNASubunit
1989
RNA Polymerase II Subunit RPB4 Is Essential for High- and Low-Temperature Yeast Cell Growth
Woychik N, Young R. RNA Polymerase II Subunit RPB4 Is Essential for High- and Low-Temperature Yeast Cell Growth. Molecular And Cellular Biology 1989, 9: 2854-2859. DOI: 10.1128/mcb.9.7.2854-2859.1989.Peer-Reviewed Original ResearchRPB4 subunitRNA polymerase II subunitEscherichia coli RNA polymeraseSequence analysis of tryptic peptidesAmino acid sequence analysis of tryptic peptidesRNA polymerase II activityAmino acid sequence analysisDeletion of RPB4Polymerase II subunitAnalysis of tryptic peptidesRNA polymerase IIAmino acidsPolymerase II activityRPB4 geneSigma subunitCrude extracts in vitroPolymerase IIRNA polymeraseSaccharomyces cerevisiaeEnzyme assemblyDNA sequencesRpb4Purified subunitsExtracts in vitroMRNA synthesis