2024
UPF1 regulates mRNA stability by sensing poorly translated coding sequences
Musaev D, Abdelmessih M, Vejnar C, Yartseva V, Weiss L, Strayer E, Takacs C, Giraldez A. UPF1 regulates mRNA stability by sensing poorly translated coding sequences. Cell Reports 2024, 43: 114074. PMID: 38625794, PMCID: PMC11259039, DOI: 10.1016/j.celrep.2024.114074.Peer-Reviewed Original ResearchConceptsUpstream open reading framesOpen reading frameRegulate mRNA stabilityNonsense-mediated decayMRNA stabilityReading frameOpen reading frame lengthRegulate mRNA decayAU-rich elementsMicroRNA binding sitesCis-elementsTranslation initiationStop codonMRNA decayCodon optimizationUPF1Gene expressionBinding sitesCodonMRNAConvergent rolesHigher decay ratesMachine-learning analysisUTR
2019
Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish
Vejnar CE, Messih M, Takacs C, Yartseva V, Oikonomou P, Christiano R, Stoeckius M, Lau S, Lee M, Beaudoin JD, Musaev D, Darwich-Codore H, Walther T, Tavazoie S, Cifuentes D, Giraldez A. Genome wide analysis of 3′ UTR sequence elements and proteins regulating mRNA stability during maternal-to-zygotic transition in zebrafish. Genome Research 2019, 29: 1100-1114. PMID: 31227602, PMCID: PMC6633259, DOI: 10.1101/gr.245159.118.Peer-Reviewed Original ResearchConceptsAU-rich elementsMRNA stabilityZygotic transitionRich motifGenome-wide analysisRNA-protein interactionsGenome activationParallel reporterCombinatorial regulationMaternal transcriptsMiR-430Destabilizing motifsRegulatory motifsWide analysisMRNA deadenylationPosttranscriptional regulationRegulatory sequencesMost transcriptsMultiple decay pathwaysUTR sequencesSequence elementsGene expressionTarget sequenceDecay pathwaysMotif
2018
Analyses of mRNA structure dynamics identify embryonic gene regulatory programs
Beaudoin JD, Novoa EM, Vejnar CE, Yartseva V, Takacs CM, Kellis M, Giraldez AJ. Analyses of mRNA structure dynamics identify embryonic gene regulatory programs. Nature Structural & Molecular Biology 2018, 25: 677-686. PMID: 30061596, PMCID: PMC6690192, DOI: 10.1038/s41594-018-0091-z.Peer-Reviewed Original ResearchConceptsGene regulatory programsUntranslated regionRegulatory programsKey maternal factorsZygotic transitionZebrafish developmentGene functionRNA functionRegulatory elementsGene expressionRNA structureRNA foldingBiological transitionsStructure dynamicsCentral roleCrucial roleCellular systemsRemodelersTranscriptomeRibosomesVivoGenesFoldingCCNA1Role
2016
Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition
Bazzini AA, del Viso F, Moreno‐Mateos M, Johnstone TG, Vejnar CE, Qin Y, Yao J, Khokha MK, Giraldez AJ. Codon identity regulates mRNA stability and translation efficiency during the maternal‐to‐zygotic transition. The EMBO Journal 2016, 35: 2087-2103. PMID: 27436874, PMCID: PMC5048347, DOI: 10.15252/embj.201694699.Peer-Reviewed Original ResearchConceptsZygotic transitionMRNA stabilityTranslation efficiencyMRNA clearanceMaternal mRNAsCodon identityCodon compositionGene expressionMaternal mRNA clearanceRegulated mRNA decayPost-transcriptional mechanismsAmino acid sequenceTranscript decayMRNA decayPolyadenylation statusAmino acid compositionCodon tripletsGenetic codeSynonymous codonsAcid sequenceCellular transitionsRegulatory informationNew transcriptionDevelopmental progressionMRNAUpstream ORFs are prevalent translational repressors in vertebrates
Johnstone TG, Bazzini AA, Giraldez AJ. Upstream ORFs are prevalent translational repressors in vertebrates. The EMBO Journal 2016, 35: 706-723. PMID: 26896445, PMCID: PMC4818764, DOI: 10.15252/embj.201592759.Peer-Reviewed Original ResearchConceptsUpstream open reading framesUntranslated mRNA regionsPost-transcriptional regulationOpen reading frameMRNA leader sequenceClear repressionVertebrate transcriptomesRibosome footprintingCellular diversityTranslational repressorIndividual genesNatural selectionUpstream ORFsReading frameLeader sequenceRegulatory potentialActive translationRegulatory codeInitiation contextGene expressionMRNA regionsUnknown functionReporter experimentsVertebratesIntercistronic distance
2013
Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition
Lee MT, Bonneau AR, Takacs CM, Bazzini AA, DiVito KR, Fleming ES, Giraldez AJ. Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Nature 2013, 503: 360-364. PMID: 24056933, PMCID: PMC3925760, DOI: 10.1038/nature12632.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCellular ReprogrammingEmbryonic DevelopmentFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalHomeodomain ProteinsMicroRNAsMothersNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsRibosomesSOXB1 Transcription FactorsTranscriptomeZebrafishZebrafish ProteinsZygoteConceptsZygotic genome activationZygotic transitionMiR-430Zygotic gene expressionZygotic gene activationZygotic developmental programMaternal messenger RNAsZygotic programGenome activationZygotic genesZygotic transcriptionRibosome profilingDevelopmental programGene activationTranscription factorsDevelopmental arrestGene expressionSoxB1POU5F1Maternal programMessenger RNANanogGastrulationZebrafishGenes
2012
Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish
Bazzini AA, Lee MT, Giraldez AJ. Ribosome Profiling Shows That miR-430 Reduces Translation Before Causing mRNA Decay in Zebrafish. Science 2012, 336: 233-237. PMID: 22422859, PMCID: PMC3547538, DOI: 10.1126/science.1215704.Peer-Reviewed Original ResearchConceptsMiR-430MRNA decayTranslational repressionMutant zebrafish embryosMessenger RNA decayNumber of ribosomesRibosome occupancyZebrafish developmentRibosome profilingTarget repressionRNA decayTranslation initiationZebrafish embryosTarget mRNAsRibosome densityEndogenous mRNAGene expressionPolyadenylate tailDeadenylationRepressionMRNAZebrafishRibosomesMicroRNAsRate of initiation
2005
MicroRNAs Regulate Brain Morphogenesis in Zebrafish
Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF. MicroRNAs Regulate Brain Morphogenesis in Zebrafish. Science 2005, 308: 833-838. PMID: 15774722, DOI: 10.1126/science.1109020.Peer-Reviewed Original ResearchConceptsRNA-binding domainMultiple cell typesDicer mutantsMutant embryosSmall RNAsPrecursor miRNAsAxis formationMature miRNAsRibonuclease IIIHeart developmentGene expressionBrain morphogenesisAbnormal morphogenesisLater stepsMiRNA formationMorphogenesisMutantsMiRNAsCell typesBrain formationEssential roleZebrafishBrain defectsSomitogenesisGastrulation