2025
Human CCR4 deadenylase homolog Angel1 is a Non-Stop mRNA Decay factor.
Nicholson-Shaw T, Dowdle M, Ajaj Y, Perelis M, Fulzele A, Yeo G, Bennett E, Lykke-Andersen J. Human CCR4 deadenylase homolog Angel1 is a Non-Stop mRNA Decay factor. RNA 2025, rna.080399.125. PMID: 40441874, DOI: 10.1261/rna.080399.125.Peer-Reviewed Original ResearchMRNA decayRibosome-associated quality controlAbsence of stop codonsQuality control pathwaysMRNA decay factorsMRNA coding regionNonsense-mediated decayTargets aberrant mRNAsNascent polypeptidesCatalytic residuesPremature polyadenylationReporter mRNAAberrant mRNAsCoding regionStabilization of reporter mRNAsStop codonAngel1Control pathwaysBiochemical activityHuman cellsCodonMRNAPathwayDecayPolyadenylationNeuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators
Malone T, Wu J, Zhang Y, Licznerski P, Chen R, Nahiyan S, Pedram M, Jonas E, Kaczmarek L. Neuronal potassium channel activity triggers initiation of mRNA translation through binding of translation regulators. Science Advances 2025, 11: eadv3140. PMID: 40435242, PMCID: PMC12118559, DOI: 10.1126/sciadv.adv3140.Peer-Reviewed Original ResearchConceptsMRNA translationTranslational regulationInitiation of mRNA translationInitiation of translationSevere intellectual disabilityRegulation of translationMRNA translation regulationNeurites of cortical neuronsB-actinChannel activityIntellectual disabilityPotassium channel activityNeuronal activityMolecular mechanismsInhibit initiationMutationsCell linesPharmacological stimulationCortical neuronsMRNABindingRegulationTranslationEIF4ECYFIP1FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia
Huang H, Li X, Luo J, Gao C, Yang M, Xu J, Xie T, Chen Z, Wang D, Wang Y, Li H, Huang J, Liu Y, Zhang H, Ntziachristos P, Zhao Y, Qing G, Liu H. FTO regulates ELK3-mediated metabolic rewiring and represents a unique therapeutic target in T cell leukemia. Science Advances 2025, 11: eadq3052. PMID: 40435251, PMCID: PMC12118595, DOI: 10.1126/sciadv.adq3052.Peer-Reviewed Original ResearchConceptsT-cell leukemiaT-ALLT-cell acute lymphoblastic leukemiaAcute lymphoblastic leukemiaExpression of glycolytic genesDevelopment of potential therapeutic strategiesPotential therapeutic strategyAntileukemia efficacyLymphoblastic leukemiaLeukemia initiationLymphoid leukemiaTherapeutic strategiesGlycolytic genesPharmacological inhibitionMetabolic rewiringLeukemiaDemethylase FTOHuman cancersN6-methyladenosineMRNA stabilityTherapeutic targetCancerMechanistic analysisMRNAModel systemDissecting the stress granule RNA world: dynamics, strategies and data
Biancon G, Busarello E, Cheng M, Halene S, Tebaldi T. Dissecting the stress granule RNA world: dynamics, strategies and data. RNA 2025, 31: rna.080409.125. PMID: 40086831, PMCID: PMC12084887, DOI: 10.1261/rna.080409.125.Peer-Reviewed Original ResearchConceptsStress granulesRNA worldRegulation of gene expressionRNA-binding proteinsCytoplasmic ribonucleoprotein granulesRibonucleoprotein granulesTranscriptome dataRNA componentSG dynamicsCell signalingSG compositionSG componentsGene expressionCellular adaptationHuman diseasesStress conditionsExperimental strategiesRNAProteinComprehensive understandingMRNAGranulesRegulationG3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration
Boraas L, Hu M, Martino P, Thornton L, Vejnar C, Zhen G, Zeng L, Parker D, Cox A, Giraldez A, Su X, Mayr C, Wang S, Nicoli S. G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration. Cell Reports 2025, 44: 115237. PMID: 39883578, PMCID: PMC11923778, DOI: 10.1016/j.celrep.2025.115237.Peer-Reviewed Original ResearchConceptsRNA-binding proteinsFocal adhesionsCell migrationStress granulesRNA-dependent mannerProtein mobilityFA proteinsRNA bindingDimerization domainSubcellular localizationRibonucleoprotein complexNon-stress conditionsFA sizeCell speedG3BP1RibonucleoproteinFA localizationBiological processesB-actinMRNAProteinCellsFA functionMigrationLocalization
2024
Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs
Lewis C, Xie L, Bhandarkar S, Jin D, Abdallah K, Draycott A, Chen Y, Thoreen C, Gilbert W. Quantitative profiling of human translation initiation reveals elements that potently regulate endogenous and therapeutically modified mRNAs. Molecular Cell 2024, 85: 445-459.e5. PMID: 39706187, PMCID: PMC11780321, DOI: 10.1016/j.molcel.2024.11.030.Peer-Reviewed Original ResearchConceptsTranslation initiationUntranslated regionHuman 5'-untranslated regionChemically modified nucleotidesHigh-throughput methodRibosome recruitmentAlternative isoformsRegulatory elementsEnhanced translationDissecting mechanismsTherapeutic mRNANucleotideTherapeutic proteinsMRNADelivery of therapeutic proteinsSequenceMRNA vaccinesEndogenous RNAQuantitative profilingWidespread effectsTranslation outputRNATherapeuticsIsoformsCellular immunogenicityArtificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy
Witten J, Raji I, Manan R, Beyer E, Bartlett S, Tang Y, Ebadi M, Lei J, Nguyen D, Oladimeji F, Jiang A, MacDonald E, Hu Y, Mughal H, Self A, Collins E, Yan Z, Engelhardt J, Langer R, Anderson D. Artificial intelligence-guided design of lipid nanoparticles for pulmonary gene therapy. Nature Biotechnology 2024, 1-10. PMID: 39658727, PMCID: PMC12149338, DOI: 10.1038/s41587-024-02490-y.Peer-Reviewed Original ResearchLipid nanoparticlesMRNA deliveryIonizable lipidsImprove nanoparticle deliveryPulmonary gene therapyDelivery in vitroNucleic acid deliveryNeural networkGene therapyNasal mucosaNanoparticle deliveryMouse lungFerret lungsAcid deliveryMouse muscleMessage-passing neural networkDelivery technologiesIn vivoLipid designLungMiceDeliveryDeep learningMRNALipidCellular translational enhancer elements that recruit eukaryotic initiation factor 3.
Koubek J, Kaur J, Bhandarkar S, Lewis C, Niederer R, Stanciu A, Aitken C, Gilbert W. Cellular translational enhancer elements that recruit eukaryotic initiation factor 3. RNA 2024, 31: 193-207. PMID: 39626887, PMCID: PMC11789482, DOI: 10.1261/rna.080310.124.Peer-Reviewed Original ResearchEukaryotic initiation factor 3Initiation factor 3Eukaryotic gene expressionTranslational enhancer elementMRNA-specific translationNative 5'-UTRFactor 3Initiation factor activityHigh-throughput approachRibosome recruitmentTranslation initiationRibosome densityBind mRNACellular mRNAsTranslational enhancerEnhancer elementsGrowing cellsGene expressionCentral playerFunctional relevanceRibosomeStress conditionsFactor activityAlternative pathwayMRNACotranslational molecular condensation of cochaperones and assembly factors facilitates axonemal dynein biogenesis
Li Y, Xu W, Cheng Y, Djenoune L, Zhuang C, Cox A, Britto C, Yuan S, Wang S, Sun Z. Cotranslational molecular condensation of cochaperones and assembly factors facilitates axonemal dynein biogenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2402818121. PMID: 39541357, PMCID: PMC11588059, DOI: 10.1073/pnas.2402818121.Peer-Reviewed Original ResearchConceptsDynein axonemal assembly factorsAssembly factorsCytosolic fociOuter dynein armsMacromolecular machinesAxonemal dyneinsAssembly hubDynein armsMolecular condensateLiquid-liquid phase separationCochaperoneEncoding mRNAFoci formationCiliary motilityStable interactionLRRC6Functional significanceRUVBL1DyneinMRNAAssembly of multiple componentsAssemblyPotential mechanismsRUVBL2BiogenesisAlternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions
Lee P, Sun Y, Soares A, Fai C, Picciotto M, Guo J. Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions. Molecular Cell 2024, 84: 3967-3978.e8. PMID: 39317199, PMCID: PMC11490368, DOI: 10.1016/j.molcel.2024.08.032.Peer-Reviewed Original ResearchTranslation initiation siteNeuronal pentraxin receptorAUG translational initiation siteAlternative translation initiation sitesN-terminal signal sequenceN-terminal transmembrane domainRNA secondary structureAlternative translation initiationN-terminal extensionTranslation initiationSignal sequenceProtein isoformsProtein localizationAUG initiatorTransmembrane domainWidespread mechanismSecondary structureInitiation siteAlternative usageAMPA-type glutamate receptorsProteoformsSecreted factorsProteinReduced AMPA receptorMRNARluA is the major mRNA pseudouridine synthase in Escherichia coli
Schaening-Burgos C, LeBlanc H, Fagre C, Li G, Gilbert W. RluA is the major mRNA pseudouridine synthase in Escherichia coli. PLOS Genetics 2024, 20: e1011100. PMID: 39241085, PMCID: PMC11421799, DOI: 10.1371/journal.pgen.1011100.Peer-Reviewed Original ResearchConceptsPseudouridine synthasesHigh-confidence sitesMRNA-modifying enzymesE. coli mRNAsStructure probing dataIdentified target sitesTarget siteDiverse eukaryotesBacterial mRNAsRNA modificationsRluAEscherichia coliSecondary structureE. coliTRNAPseudouridineRRNAStructural motifsMRNAModification capacityRecognition elementsSynthaseRNASequenceEukaryotesSalp14 epitope-based mRNA vaccination induces early recognition of a tick bite
Cui Y, Cibichakravarthy B, Tang X, Alameh M, Dwivedi G, Weissman D, Fikrig E. Salp14 epitope-based mRNA vaccination induces early recognition of a tick bite. Vaccine 2024, 42: 126304. PMID: 39236403, PMCID: PMC11416896, DOI: 10.1016/j.vaccine.2024.126304.Peer-Reviewed Original ResearchTick bite siteGuinea pigsMRNA-LNPMRNA vaccinesBite siteImmunized guinea pigsTiters of IgGIxodes scapularis ticksDevelopment of erythemaLipid nanoparticlesSkin of guinea pigsI. scapularisTicksErythemaHistamine activityPigsTick bitesCarboxyl terminusRepeated exposureExposure of animalsAmino acidsSalivary proteinsVaccineMRNAGuineaBranching in poly(amine-co-ester) polyplexes impacts mRNA transfection
Shin K, Suh H, Suberi A, Whang C, Ene M, Grundler J, Grun M, Saltzman W. Branching in poly(amine-co-ester) polyplexes impacts mRNA transfection. Biomaterials 2024, 311: 122692. PMID: 38986360, PMCID: PMC11298310, DOI: 10.1016/j.biomaterials.2024.122692.Peer-Reviewed Original ResearchPolymer branchingTransfection in vivoPhysicochemical propertiesPoly(amine-co-esterMRNA deliveryTerminal groupsPolymer featuresIn vitroPolymerNucleic acid deliveryMonomer compositionAnalysis of physicochemical propertiesStructural parametersCationic polymersStability of polyplexesMRNA transfectionTransfection efficiencyAcid deliveryDelivery vehiclesTransfectionMRNAUPF1 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 analysisUTRRecent developments, opportunities, and challenges in the study of mRNA pseudouridylation
Gilbert W. Recent developments, opportunities, and challenges in the study of mRNA pseudouridylation. RNA 2024, 30: rna.079975.124. PMID: 38531650, PMCID: PMC11019745, DOI: 10.1261/rna.079975.124.Peer-Reviewed Original Research
2023
Normalizing need not be the norm: count-based math for analyzing single-cell data
Church S, Mah J, Wagner G, Dunn C. Normalizing need not be the norm: count-based math for analyzing single-cell data. Theory In Biosciences 2023, 143: 45-62. PMID: 37947999, DOI: 10.1007/s12064-023-00408-x.Peer-Reviewed Original ResearchMaster transcription factor reprograming unleashes selective translation promoting castration resistance and immune evasion in lethal prostate cancer.
Santasusagna S, Zhu S, Jawalagatti V, Carceles-Cordon M, Ertel A, Garcia-Longarte S, Song W, Fujiwara N, Li P, Mendizabal I, Petrylak D, Kelly W, Reddy E, Wang L, Schiewer M, Lujambio A, Karnes J, Knudsen K, Cordon-Cardo C, Dong H, Huang H, Carracedo A, Hoshida Y, Rodriguez-Bravo V, Domingo-Domenech J. Master transcription factor reprograming unleashes selective translation promoting castration resistance and immune evasion in lethal prostate cancer. Cancer Discovery 2023, 13: 2584-2609. PMID: 37676710, PMCID: PMC10714140, DOI: 10.1158/2159-8290.cd-23-0306.Peer-Reviewed Original ResearchConceptsLethal prostate cancerProstate cancerCastration resistanceImmune evasionPharmacologic targetingAnti-PD-1 therapyMajor histocompatibility complex IDeprivation therapyMicrophthalmia transcription factorAndrogen receptorPreclinical modelsTherapeutic strategiesCancerTherapyDruggable mechanismMaster transcription factorTranscription factorsKey mRNAsSpecific mRNAsMRNAFactor 3bEvasionSelected ArticlesTargetingTumorsPolymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic deliveryTracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNAStress promotes RNA G-quadruplex folding in human cells
Kharel P, Fay M, Manasova E, Anderson P, Kurkin A, Guo J, Ivanov P. Stress promotes RNA G-quadruplex folding in human cells. Nature Communications 2023, 14: 205. PMID: 36639366, PMCID: PMC9839774, DOI: 10.1038/s41467-023-35811-x.Peer-Reviewed Original ResearchConceptsHuman cellsMRNA stabilityCellular stress responseRG4 structuresG-quadruplex structuresRNA G4sDynamic regulationG-quadruplex foldingRich nucleic acidsStress responsePermissive conditionsRG4FoldingStress removalRegulatory impactNucleic acidsCellsDimethylsulfateRNAMotifGuanineMRNARegulationStressSequence
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