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
Induced 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
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