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 expressionTranslation
2017
La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region
Philippe L, Vasseur JJ, Debart F, Thoreen CC. La-related protein 1 (LARP1) repression of TOP mRNA translation is mediated through its cap-binding domain and controlled by an adjacent regulatory region. Nucleic Acids Research 2017, 46: gkx1237-. PMID: 29244122, PMCID: PMC5814973, DOI: 10.1093/nar/gkx1237.Peer-Reviewed Original ResearchMeSH KeywordsAutoantigensBase SequenceBinding SitesBinding, CompetitiveCell-Free SystemComputational BiologyEukaryotic Initiation Factor-4FGene Expression RegulationHEK293 CellsHumansMechanistic Target of Rapamycin Complex 1Models, GeneticPolyribosomesProtein BindingProtein BiosynthesisProtein Interaction Domains and MotifsPyrimidinesRibonucleoproteinsRNA, MessengerConceptsTOP mRNA translationAdjacent regulatory regionsMRNA translationCap-binding domainCap structureRegulatory regionsEukaryotic initiation factor 4FMRNA 5' cap structureIntrinsic repressive activityTerminal oligopyrimidine motifsInitiation factor 4FMRNA 5' endsC-terminal halfGrowth-related mRNAsTOP mRNAsRepressive activityTranslation factorsMRNA targetsCoordinated changesGene expressionLARP1Cell growthProtein 1Top sequenceMRNAmTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4
Park Y, Reyna-Neyra A, Philippe L, Thoreen CC. mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4. Cell Reports 2017, 19: 1083-1090. PMID: 28494858, PMCID: PMC5811220, DOI: 10.1016/j.celrep.2017.04.042.Peer-Reviewed Original ResearchConceptsUpstream open reading framesATF4 translationTranscriptional programsProtein synthesisEukaryotic initiation factor 2 alphaInitiation factor 2 alphaPost-transcriptional controlRapamycin complex 1Open reading frameIntegrated stress responseAmino acid transportersTranscription factor 4Translation machineryTranslation repressorProtein familyReading frameMaster regulatorPromoter elementsBioinformatics analysisResponsive mRNAsAmino acid supplyStress responseMetabolic enzymesKey effectorsAcid transporters
2012
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen CC, Chantranupong L, Keys HR, Wang T, Gray NS, Sabatini DM. A unifying model for mTORC1-mediated regulation of mRNA translation. Nature 2012, 485: 109-113. PMID: 22552098, PMCID: PMC3347774, DOI: 10.1038/nature11083.Peer-Reviewed Original Research5' Untranslated RegionsAnimalsBase SequenceCell Line, TumorEukaryotic Initiation Factor-4EEukaryotic Initiation Factor-4GGene Expression RegulationHumansMaleMechanistic Target of Rapamycin Complex 1MiceModels, BiologicalMultiprotein ComplexesNaphthyridinesNucleotide MotifsPhosphorylationProstatic NeoplasmsProtein BindingProtein BiosynthesisProteinsRibosomesRNA, MessengerTOR Serine-Threonine Kinases