2024
Maternal regulation of the vertebrate oocyte-to-embryo transition
Fuentes R, Marlow F, Abrams E, Zhang H, Kobayashi M, Gupta T, Kapp L, DiNardo Z, Heller R, Cisternas R, García-Castro P, Segovia-Miranda F, Montecinos-Franjola F, Vought W, Vejnar C, Giraldez A, Mullins M. Maternal regulation of the vertebrate oocyte-to-embryo transition. PLOS Genetics 2024, 20: e1011343. PMID: 39052672, PMCID: PMC11302925, DOI: 10.1371/journal.pgen.1011343.Peer-Reviewed Original ResearchOocyte-to-embryo transitionMutant geneZebrafish forward genetic screenEgg activationForward genetic screensGenetic entry pointsMaternal-effect mutantsBasic body planCytoplasmic segregationBody planIntracellular traffickingGenetic screeningMicrotubule nucleationProtein cleavageMaternal genesVesicle formationGenesFunctional importanceHuman diseasesMolecular mechanismsMolecular insightsCortical granulesBlack caviarMaternal regulationMolecular natureUPF1 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
2022
The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation
Miao L, Tang Y, Bonneau AR, Chan SH, Kojima ML, Pownall ME, Vejnar CE, Gao F, Krishnaswamy S, Hendry CE, Giraldez AJ. The landscape of pioneer factor activity reveals the mechanisms of chromatin reprogramming and genome activation. Molecular Cell 2022, 82: 986-1002.e9. PMID: 35182480, PMCID: PMC9327391, DOI: 10.1016/j.molcel.2022.01.024.Peer-Reviewed Original ResearchConceptsGenome activationChromatin openingTranscription factorsPioneer factor activityDifferent transcription factorsChromatin reprogrammingPioneer factorsNucleosome positionsActive enhancersIndividual genesCore histonesTriple mutantGene activationTF inputsDevelopmental transitionsSequence contextCell typesFactor activityHistonesPioneering activityEnhancerActivationSequence of eventsPou5f3Chromatin
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 pathwaysMotifBrd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation
Chan SH, Tang Y, Miao L, Darwich-Codore H, Vejnar CE, Beaudoin JD, Musaev D, Fernandez JP, Benitez MDJ, Bazzini AA, Moreno-Mateos MA, Giraldez AJ. Brd4 and P300 Confer Transcriptional Competency during Zygotic Genome Activation. Developmental Cell 2019, 49: 867-881.e8. PMID: 31211993, PMCID: PMC7201981, DOI: 10.1016/j.devcel.2019.05.037.Peer-Reviewed Original ResearchConceptsGenome activationTranscriptional competencyHistone acetylationP300-dependent histone acetylationZygotic genome activationFirst zygotic genesMaternal mRNA translationZygotic genesAnimal developmentZygotic developmentDevelopmental reprogrammingMRNA translationLive imagingCell cycleSilent genomeBRD4ZebrafishGenomeTranscriptionAcetylationActivationP300FertilizationReprogrammingGenes
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
RESA identifies mRNA-regulatory sequences at high resolution
Yartseva V, Takacs CM, Vejnar CE, Lee MT, Giraldez AJ. RESA identifies mRNA-regulatory sequences at high resolution. Nature Methods 2016, 14: 201-207. PMID: 28024160, PMCID: PMC5423094, DOI: 10.1038/nmeth.4121.Peer-Reviewed Original ResearchCodon 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
2015
CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo
Moreno-Mateos MA, Vejnar CE, Beaudoin JD, Fernandez JP, Mis EK, Khokha MK, Giraldez AJ. CRISPRscan: designing highly efficient sgRNAs for CRISPR-Cas9 targeting in vivo. Nature Methods 2015, 12: 982-988. PMID: 26322839, PMCID: PMC4589495, DOI: 10.1038/nmeth.3543.Peer-Reviewed Original Research
2014
Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation
Bazzini AA, Johnstone TG, Christiano R, Mackowiak SD, Obermayer B, Fleming ES, Vejnar CE, Lee MT, Rajewsky N, Walther TC, Giraldez AJ. Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. The EMBO Journal 2014, 33: 981-993. PMID: 24705786, PMCID: PMC4193932, DOI: 10.1002/embj.201488411.Peer-Reviewed Original Research
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
2010
A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity
Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND, Wolfe SA, Giraldez AJ. A Novel miRNA Processing Pathway Independent of Dicer Requires Argonaute2 Catalytic Activity. Science 2010, 328: 1694-1698. PMID: 20448148, PMCID: PMC3093307, DOI: 10.1126/science.1190809.Peer-Reviewed Original ResearchAnimalsArgonaute ProteinsBiocatalysisEmbryo, NonmammalianEmbryonic DevelopmentErythropoiesisEukaryotic Initiation Factor-2HumansMicroRNAsModels, BiologicalMorphogenesisNucleic Acid ConformationRecombinant ProteinsRibonuclease IIIRNA PrecursorsRNA Processing, Post-TranscriptionalZebrafishZebrafish Proteins
2008
MicroRNAs in Development and Disease
Staton A, Giraldez A. MicroRNAs in Development and Disease. 2008 DOI: 10.1002/9780470015902.a0020863.Peer-Reviewed Original Research
2006
Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs
Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF. Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs. Science 2006, 312: 75-79. PMID: 16484454, DOI: 10.1126/science.1122689.Peer-Reviewed Original ResearchMeSH Keywords3' Untranslated RegionsAdenosineAnimalsEmbryo, NonmammalianEmbryonic DevelopmentFemaleGene Expression ProfilingGene Expression Regulation, DevelopmentalGenes, ReporterGreen Fluorescent ProteinsMicroRNAsMutationOligonucleotide Array Sequence AnalysisPolymersProtein BiosynthesisRibonuclease IIIRNA StabilityRNA, MessengerTranscription, GeneticUp-RegulationZebrafishZygoteConceptsMessenger RNA moleculesTarget messenger RNA moleculesMiR-430Vivo target validationVertebrate genesZygotic transcriptionEarly embryogenesisRNA moleculesMicroarray approachVivo functionDeadenylationTarget validationEarly developmentMechanism of actionMost targetsEmbryogenesisMorphogenesisTranscriptionGenesMicroRNAsTarget
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