2022
mRNA 5′ terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay
van den Elzen A, Watson M, Thoreen C. mRNA 5′ terminal sequences drive 200-fold differences in expression through effects on synthesis, translation and decay. PLOS Genetics 2022, 18: e1010532. PMID: 36441824, PMCID: PMC9731452, DOI: 10.1371/journal.pgen.1010532.Peer-Reviewed Original ResearchConceptsTerminal sequenceGene expressionKey post-transcriptional regulatorsTerminal oligopyrimidine motifsCore promoter motifsPost-transcriptional regulatorsPromoter motifsMRNA decayTranslation initiationRegulatory sequencesReporter mRNAEfficient transcriptionLibrary sequencesEndogenous mRNARegulatory potentialNative mRNAHuman cellsTranscriptionMRNAHybrid sequencesSequenceExpressionMotifMRNA expressionTranslationMeasuring 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
2020
Roadblock-qPCR: a simple and inexpensive strategy for targeted measurements of mRNA stability
Watson M, Park Y, Thoreen C. Roadblock-qPCR: a simple and inexpensive strategy for targeted measurements of mRNA stability. RNA 2020, 27: 335-342. PMID: 33288682, PMCID: PMC7901842, DOI: 10.1261/rna.076885.120.Peer-Reviewed Original ResearchInduced pluripotent stem cell reprogramming‐associated methylation at the GABRA2 promoter and chr4p12 GABAA subunit gene expression in the context of alcohol use disorder
Goetjen A, Watson M, Lieberman R, Clinton K, Kranzler H, Covault J. Induced pluripotent stem cell reprogramming‐associated methylation at the GABRA2 promoter and chr4p12 GABAA subunit gene expression in the context of alcohol use disorder. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2020, 183: 464-474. PMID: 33029895, PMCID: PMC8022112, DOI: 10.1002/ajmg.b.32824.Peer-Reviewed Original ResearchConceptsGene expressionSubunit gene expressionSubunit geneNeural culturesInduced pluripotent stem cellsReceptor subunit genesPluripotent stem cellsStochastic methylationGene clusterDNA methylationCpG methylationMethylation levelsReceptor subunit gene expressionMethylationSignificant genetic contributionGenesStem cellsGenetic contributionMolecular effectsIPSC linesGABRB1 geneExpressionGABRA2GenotypesAdditive effectGlobal analysis of LARP1 translation targets reveals tunable and dynamic features of 5′ TOP motifs
Philippe L, van den Elzen AMG, Watson MJ, Thoreen CC. Global analysis of LARP1 translation targets reveals tunable and dynamic features of 5′ TOP motifs. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 5319-5328. PMID: 32094190, PMCID: PMC7071917, DOI: 10.1073/pnas.1912864117.Peer-Reviewed Original ResearchConceptsTOP mRNAsTerminal oligopyrimidine motifsTranslation targetsAlternative transcription initiation sitesTOP mRNA translationRNA-binding proteinSpecific biological contextMTOR complex 1Transcription initiation siteTop sequenceTranscriptome scaleTranslation regulatorsMRNA translationRegulatory sequencesTranslation factorsTOP motifGene expressionMRNA regulationBiological contextMammalian tissuesInitiation siteProtein 1TranscriptomeLARP1MRNA
2014
Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl
Ma XM, Miller MB, Vishwanatha KS, Gross MJ, Wang Y, Abbott T, Lam TT, Mains RE, Eipper BA. Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl. Molecular Biology Of The Cell 2014, 25: 1458-1471. PMID: 24600045, PMCID: PMC4004595, DOI: 10.1091/mbc.e13-04-0215.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalpainCells, CulturedDendritic SpinesGuanine Nucleotide Exchange FactorsHippocampusMice, KnockoutNeuronsOncogene Proteins v-ablPeptide FragmentsPhosphatidylinositolsPhosphorylationProtein Processing, Post-TranslationalProtein Structure, TertiaryProteolysisRats, Sprague-DawleySynapsesTransferrinConceptsGDP/GTP exchange factorSec14 domainSpectrin repeatsSpine morphogenesisNon-receptor tyrosine kinaseGTP exchange factorSpine formationNatural splice variantSpectrin repeat domainReceptor-mediated endocytosisRho GDP/GTP exchange factorDrosophila orthologueMembrane traffickingPhosphomimetic mutationExchange factorCalpain-mediated degradationRepeat domainTruncation mutantsTyrosine kinaseGenetic studiesCellular membranesSplice variantsRepeatsNonneuronal cellsMorphogenesis
2013
Six Innexins Contribute to Electrical Coupling of C. elegans Body-Wall Muscle
Liu P, Chen B, Altun Z, Gross M, Shan A, Schuman B, Hall D, Wang Z. Six Innexins Contribute to Electrical Coupling of C. elegans Body-Wall Muscle. PLOS ONE 2013, 8: e76877. PMID: 24130800, PMCID: PMC3793928, DOI: 10.1371/journal.pone.0076877.Peer-Reviewed Original ResearchConceptsUNC-9Body wall musclesC. elegans body wall muscleBody wall muscle cellsGap junctionsEpitope-tagged proteinsInnexinsTriple mutantPunctate localizationFunctions cellMutantsIntercellular junctionsDistinct populationsMuscle expressionGFPMuscle cellsJunctional currentsElectrical couplingFunctional propertiesCellsPromoterProteinSolid foundationExpressionPopulationAnr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence
Jackson A, Gross M, Daniels E, Hampton T, Hammond J, Vallet-Gely I, Dove S, Stanton B, Hogan D. Anr and Its Activation by PlcH Activity in Pseudomonas aeruginosa Host Colonization and Virulence. Journal Of Bacteriology 2013, 195: 3093-3104. PMID: 23667230, PMCID: PMC3697539, DOI: 10.1128/jb.02169-12.Peer-Reviewed Original ResearchConceptsANR activityGlycine betainePlcH activityBiofilm formationHemolytic phospholipase CEnhanced biofilm formationGlucose-containing mediumP. aeruginosa PAO1Host colonizationLow oxygen tensionWild typeAbiotic surfacesMicroarray analysisAeruginosa PAO1Epithelial cell monolayersAbundant lipidsLines of evidenceAddition of cholinePhospholipase CCell membraneVirulenceBacterial metabolismProtein levelsMutantsRespiratory activity
2012
Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability
Filkins L, Hampton T, Gifford A, Gross M, Hogan D, Sogin M, Morrison H, Paster B, O'Toole G. Prevalence of Streptococci and Increased Polymicrobial Diversity Associated with Cystic Fibrosis Patient Stability. Journal Of Bacteriology 2012, 194: 4709-4717. PMID: 22753064, PMCID: PMC3415522, DOI: 10.1128/jb.00566-12.Peer-Reviewed Original ResearchConceptsDiverse microbial communitiesHigher bacterial diversityCystic fibrosis lung environmentQuantitative PCRGenomic DNA samplesCystic fibrosis patientsMicrobial communitiesRRNA geneBacterial communitiesBacterial diversityOverall diversityTaxonomic profilesGroup speciesMicroarray analysisDominant organismsPseudomonas aeruginosaPatient stabilityPredominant generaFibrosis patientsSpeciesHypervariable regionSpecies of StreptococcusCurrent dogmaStable lung diseaseDiversity
2011
Hemolytic Phospholipase C Inhibition Protects Lung Function during Pseudomonas aeruginosa Infection
Wargo M, Gross M, Rajamani S, Allard J, Lundblad L, Allen G, Vasil M, Leclair L, Hogan D. Hemolytic Phospholipase C Inhibition Protects Lung Function during Pseudomonas aeruginosa Infection. American Journal Of Respiratory And Critical Care Medicine 2011, 184: 345-354. PMID: 21562128, PMCID: PMC3175536, DOI: 10.1164/rccm.201103-0374oc.Peer-Reviewed Original ResearchConceptsLung functionP. aeruginosa infectionAeruginosa infectionSignificant lung function impairmentLung function impairmentLung function declineBronchoalveolar lavage fluidPseudomonas aeruginosa infectionChronic lung infectionVirulence factorsP. aeruginosaP. aeruginosa virulence factorsPulmonary surfactant functionSingle virulence factorFunction declineMechanical ventilationFunction impairmentLavage fluidRespiratory endpointsSurfactant dysfunctionComputer-controlled ventilatorLung infectionAeruginosa virulence factorsStrain infectionLung physiology
2008
GbdR Regulates Pseudomonas aeruginosa plcH and pchP Transcription in Response to Choline Catabolites
Wargo M, Ho T, Gross M, Whittaker L, Hogan D. GbdR Regulates Pseudomonas aeruginosa plcH and pchP Transcription in Response to Choline Catabolites. Infection And Immunity 2008, 77: 1103-1111. PMID: 19103776, PMCID: PMC2643652, DOI: 10.1128/iai.01008-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAraC Transcription FactorBetaineCholineDNA Mutational AnalysisElectrophoretic Mobility Shift AssayGene Expression Regulation, BacterialMaleMiceMice, Inbred C57BLPhosphoric Monoester HydrolasesPhosphorylcholinePromoter Regions, GeneticPseudomonas aeruginosaPseudomonas InfectionsReverse Transcriptase Polymerase Chain ReactionSarcosineTranscription, GeneticTransferases (Other Substituted Phosphate Groups)ConceptsGlycine betainePlcH activityAraC family transcription factorElectrophoretic mobility shift assaysFamily transcription factorsEukaryotic cell membranesHemolytic phospholipase CMobility shift assaysP. aeruginosa virulenceProtein fusionsPromoter mappingTranscriptional activationTranscription factorsGbdRPhosphorylcholine phosphatasePromoter sequencesShift assaysGene expressionPromoter mutantsFeedback inductionMutantsTranscriptionPhospholipase CPrimary regulatorCell membrane