2025
Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase
Devarkar S, Budding C, Pathirage C, Kavoor A, Herbert C, Limbach P, Musier-Forsyth K, Xiong Y. Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase. Nucleic Acids Research 2025, 53: gkaf114. PMID: 40036503, PMCID: PMC11878792, DOI: 10.1093/nar/gkaf114.Peer-Reviewed Original ResearchConceptsTransfer ribonucleic acidHuman lysyl-tRNA synthetaseLysyl-tRNA synthetaseHigh-resolution cryo-electron microscopyPost-transcriptional modificationsCryo-electron microscopyD-loopCatalytic stepStructural basisAminoacylationCryo-EMProtein synthesisCatalytic efficiencyFunctional impactSynthetaseRibonucleic acidActive siteMachineryLysRSMetazoansMs2t6ATRNALys3Mcm5s2UR37Integral roleMolecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse
Hanke-Gogokhia C, Zapadka T, Finkelstein S, Arshavsky V, Demb J. Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse. Advances In Experimental Medicine And Biology 2025, 1468: 325-330. PMID: 39930217, DOI: 10.1007/978-3-031-76550-6_54.Peer-Reviewed Original ResearchConceptsSynaptic vesicle exocytosisSynaptic vesicle recyclingPhotoreceptor ribbon synapseVesicle exocytosisVesicle recyclingVesicle cycleVesicle releaseRibbon synapseProtein synthesisProperties of synaptic transmissionMolecular componentsMouse rodsSynaptic terminalsRod cellsProteinVesiclesRod photoreceptorsDim lightSynaptic transmissionInner segmentsCellsExocytosisEndocytosisOuter segmentsEnergy production
2024
Human HDAC6 senses valine abundancy to regulate DNA damage
Jin J, Meng T, Yu Y, Wu S, Jiao C, Song S, Li Y, Zhang Y, Zhao Y, Li X, Wang Z, Liu Y, Huang R, Qin J, Chen Y, Cao H, Tan X, Ge X, Jiang C, Xue J, Yuan J, Wu D, Wu W, Jiang C, Wang P. Human HDAC6 senses valine abundancy to regulate DNA damage. Nature 2024, 637: 215-223. PMID: 39567688, DOI: 10.1038/s41586-024-08248-5.Peer-Reviewed Original ResearchConceptsHuman histone deacetylase 6Active DNA demethylationDNA demethylationValine deprivationDNA damageTen-eleven translocationRegulating DNA damageHistone deacetylase 6Repeat domainTherapeutic efficacy of PARP inhibitorsBind valineEfficacy of PARP inhibitorsCellular functionsPatient-derived xenograft modelsCytoplasmic shuttlingInduce DNA damageBranched amino acidsProtein synthesisAmino acidsIntracellular levelsPARP inhibitorsDNALevels of valineTumor growthTherapeutic efficacyApplications of cell free protein synthesis in protein design
Thornton E, Paterson S, Stam M, Wood C, Laohakunakorn N, Regan L. Applications of cell free protein synthesis in protein design. Protein Science 2024, 33: e5148. PMID: 39180484, PMCID: PMC11344276, DOI: 10.1002/pro.5148.Peer-Reviewed Original ResearchProtein folding and quality control during nuclear transport
Mallik S, Poch D, Burick S, Schlieker C. Protein folding and quality control during nuclear transport. Current Opinion In Cell Biology 2024, 90: 102407. PMID: 39142062, DOI: 10.1016/j.ceb.2024.102407.Peer-Reviewed Original ResearchProtein foldingNuclear transportCo-translational transportProtein-folding environmentAggregation of folding intermediatesProtein quality controlNuclear import machineryNuclear pore complexFolding environmentImport machineryNuclear importCytosolic aggregatesContext of neurological disordersNuclear compartmentPore complexProtein synthesisProteinQuality controlFoldingBarrier functionEvolution of transport systemsKaryopherinNucleoporinsCompartmentTemporal coordinationA Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation
Bonetti L, Horkova V, Grusdat M, Longworth J, Guerra L, Kurniawan H, Franchina D, Soriano-Baguet L, Binsfeld C, Verschueren C, Spath S, Ewen A, Koncina E, Gérardy J, Kobayashi T, Dostert C, Farinelle S, Härm J, Fan Y, Chen Y, Harris I, Lang P, Vasiliou V, Waisman A, Letellier E, Becher B, Mittelbronn M, Brenner D. A Th17 cell-intrinsic glutathione/mitochondrial-IL-22 axis protects against intestinal inflammation. Cell Metabolism 2024, 36: 1726-1744.e10. PMID: 38986617, DOI: 10.1016/j.cmet.2024.06.010.Peer-Reviewed Original ResearchReactive oxygen speciesMitochondrial functionCatalytic subunit of glutamate cysteine ligaseMitochondrial gene expressionDecreased cellular ATPPhosphorylation of 4E-BP1Disrupt mitochondrial functionReduced phosphorylation of 4E-BP1T cell-specific ablationCell's antioxidant mechanismsCell-specific ablationCatalytic subunitIL-22Cellular signalingIntestinal homeostasisIL-22 productionSignificant reactive oxygen speciesSubunit of glutamate cysteine ligaseGene expressionReduced IL-22 productionReduced phosphorylationCellular ATPGut protectionProtein synthesisGlutamate cysteine ligaseThe cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis
McCool M, Bryant C, Abriola L, Surovtseva Y, Baserga S. The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis. PLOS Biology 2024, 22: e3002718. PMID: 38976757, PMCID: PMC11257408, DOI: 10.1371/journal.pbio.3002718.Peer-Reviewed Original ResearchRibosome biogenesis factorsRibosome biogenesisBiogenesis factorsCell growthNucleolar functionRegulation of nucleolar functionHuman ribosome biogenesisProtein synthesisProduction of ribosomesFamily of proteinsSource of mutagenesisLevel of protein synthesisCytidine deaminase familyIncreased cell growthPromote cell growthPre-rRNAPotential direct rolePre-mRNATransient overexpressionRibosomeGenomic mutationsBiogenesisMCF10A cellsMaturation stepsAPOBEC3AMtb-Selective 5‑Aminomethyl Oxazolidinone Prodrugs: Robust Potency and Potential Liabilities
Boshoff H, Young K, Ahn Y, Yadav V, Crowley B, Yang L, Su J, Oh S, Arora K, Andrews J, Manikkam M, Sutphin M, Smith A, Weiner D, Piazza M, Fleegle J, Gomez F, Dayao E, Prideaux B, Zimmerman M, Kaya F, Sarathy J, Tan V, Via L, Tschirret-Guth R, Lenaerts A, Robertson G, Dartois V, Olsen D, Barry C. Mtb-Selective 5‑Aminomethyl Oxazolidinone Prodrugs: Robust Potency and Potential Liabilities. ACS Infectious Diseases 2024, 10: 1679-1695. PMID: 38581700, DOI: 10.1021/acsinfecdis.4c00025.Peer-Reviewed Original ResearchConceptsLinezolid-resistant mutantsDrug-resistant patientsAntitubercular activityN-acetyl metaboliteOxazolidinone prodrugMechanism of actionC3HeB/FeJ miceAntimycobacterial activityN-acetyl transferaseSusceptible to inhibitionCross-resistanceOxazolidinoneCompoundsMoleculesMammalian metabolismN-acetyltransferaseProdrugToxicityMoietyProtein synthesisLinezolidC3HeB/FeJCaseumPatientsLiving cellsChaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis
Chan C, Groisman E. Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis. PLOS Biology 2024, 22: e3002560. PMID: 38574172, PMCID: PMC10994381, DOI: 10.1371/journal.pbio.3002560.Peer-Reviewed Original ResearchConceptsRibosome associationProtein synthesisProtein homeostasisS. typhimuriumProtein folding capacityPreventing protein aggregationC-terminal amino acidsDomains of lifeProtein synthesis in vitroInhibit protein synthesisFolding capacityHsp70 chaperonesJ-domainSynthesis in vitroProtein foldingReduction of protein synthesisChaperone Hsp70DnaKRibosomeProtein aggregationChaperoneAmino acidsProteinStarvationHSP70
2023
RNA m6A methylation in psychiatric disorders.
Mao Q, Luo J, Luo X, Zhu X, Wang K, Zuo L, Zhang Y, Luo X. RNA m6A methylation in psychiatric disorders. EC Psychology And Psychiatry 2023, 12 PMID: 38145106, PMCID: PMC10745284.Peer-Reviewed Original ResearchMajor psychiatric disordersPsychiatric disordersM6A modificationM6A methyltransferase METTL3Synaptic protein synthesisInflammatory infiltrationImmune infiltrationRNA m6A methylationTherapeutic targetM6A regulatorsAlzheimer's diseaseNeuropsychiatric disordersMethyltransferase METTL3Subtype classificationPromising targetDiseaseDisordersM6A methylationInfiltrationCritical roleProtein synthesisReviewPathogenesisComprehensive reviewPreventionHuman nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing
McCool M, Bryant C, Huang H, Ogawa L, Farley-Barnes K, Sondalle S, Abriola L, Surovtseva Y, Baserga S. Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing. RNA Biology 2023, 20: 257-271. PMID: 37246770, PMCID: PMC10228412, DOI: 10.1080/15476286.2023.2217392.Peer-Reviewed Original ResearchConceptsPre-rRNA accumulationRibosome biogenesisNonessential roleEukaryotic ribosome biogenesisEssential cellular processesNucleolar stress responsePre-rRNA levelsRRNA processingLikely orthologCellular processesAssociated proteinsTumor suppressorStress responseHuman cellsProtein synthesisProtein 7Human counterpartBiogenesisYeastOrthologsHomologSubcomplexAccumulationRRNATranscriptionMapping the in vivo fitness landscape of a tethered ribosome
Radford F, Rinehart J, Isaacs F. Mapping the in vivo fitness landscape of a tethered ribosome. Science Advances 2023, 9: eade8934. PMID: 37115918, PMCID: PMC10146877, DOI: 10.1126/sciadv.ade8934.Peer-Reviewed Original ResearchConceptsPeptidyl transfer centerEpistatic interactionsFitness landscapeMacromolecular machinesLaboratory evolutionRibosome functionDeleterious mutationsVivo fitness landscapeComplete mutagenesisLethal mutationsGenetic elementsRibosomesProtein synthesisDominant lethal mutationsMost nucleotidesMutationsSequence spaceNucleotidesNext-generation biomaterialsLandscapeMutagenesisOrganismsSequenceInteractionDeeper understandingEpigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis
Li M, Yang L, Chan A, Pokharel S, Liu Q, Mattson N, Xu X, Chang W, Miyashita K, Singh P, Zhang L, Li M, Wu J, Wang J, Chen B, Chan L, Lee J, Zhang X, Rosen S, Müschen M, Qi J, Chen J, Hiom K, Bishop A, Chen C. Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1‐EEF1A1 Axis. Advanced Science 2023, 10: 2206584. PMID: 37075745, PMCID: PMC10265057, DOI: 10.1002/advs.202206584.Peer-Reviewed Original ResearchConceptsProtein translation machineryHistone H4 acetylationOncogenic transcription factorNuA4 histoneChromatin remodelersGene bodiesEpigenetic networksTranslation machineryATPase componentEpigenetic controlTumor progressionCRISPR screensTranscription factorsH4 acetylationEpigenetic dysregulationRUVBL1Oncogenic signalingProtein synthesisPatient-derived samplesMYCPharmacological inhibitionEEF1A1 expressionMultiple cancersNovel opportunitiesDynamic interplay3189 – REVISITING THE HEMATOPOIETIC AND ERYTHROPOIETIC DEFECTS IN RPS19 AND RPL5 HAPLOINSUFFICIENCY AT THE DEVELOPMENTAL LEVEL
Tang Y, Ling T, Durand S, Palis J, Steiner L, Mohandas N, Gallagher P, Lipton J, Crispino J, Blanc L. 3189 – REVISITING THE HEMATOPOIETIC AND ERYTHROPOIETIC DEFECTS IN RPS19 AND RPL5 HAPLOINSUFFICIENCY AT THE DEVELOPMENTAL LEVEL. Experimental Hematology 2023, 124: s144. DOI: 10.1016/j.exphem.2023.06.296.Peer-Reviewed Original ResearchRibosomal proteinsDiamond-Blackfan anemiaGlobal protein synthesisTerminal erythroid differentiationStem cell exhaustionHematopoietic stem cell exhaustionKey transcription factorInherited bone marrow failure syndromeFailure of erythropoiesisCell cycle arrestHematopoietic developmentMutant cellsTranscription factorsProgenitor stageCRISPR/Erythroid differentiationVav-iCreMendelian ratioDefective erythropoiesisRPS19Bone marrow failure syndromesLoxP sitesProtein synthesisBone marrow failureHematopoietic progenitors
2022
Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity
Han W, Peng B, Wang C, Townsend G, Barry N, Peske F, Goodman A, Liu J, Rodnina M, Groisman E. Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity. The EMBO Journal 2022, 42: embj2022112372. PMID: 36472247, PMCID: PMC9841332, DOI: 10.15252/embj.2022112372.Peer-Reviewed Original ResearchConceptsEF-G1Protein synthesisGTPase activityGuanosine triphosphateElongation factor GCarbon starvationCellular processesStarvation conditionsBacteroides thetaiotaomicronFactor GSingular abilityAmino acidsCell growthParalogsMurine cecumTranslocationGut colonizationColonizationCellsRibosomesProteinStarvationThetaiotaomicronBacteriaFitnessHuman pre-60S assembly factors link rRNA transcription to pre-rRNA processing
McCool M, Buhagiar A, Bryant C, Ogawa L, Abriola L, Surovtseva Y, Baserga S. Human pre-60S assembly factors link rRNA transcription to pre-rRNA processing. RNA 2022, 29: rna.079149.122. PMID: 36323459, PMCID: PMC9808572, DOI: 10.1261/rna.079149.122.Peer-Reviewed Original ResearchRRNA transcriptionRRNA processingRibosomal subunit biogenesisRNA polymerase IRibosome biosynthesisSubunit biogenesisRibosome biogenesisRibosome assemblyAssembly factorsTranscription controlBiogenesis factorsRRNA productionSteady-state levelsRNA transcriptionPolymerase IComplex membersHuman cellsProtein synthesisP53 stabilizationTranscriptionEssential processBiogenesisCell proliferationDual roleRegulatory detailstRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis
Liu Y, Zhou J, Li X, Zhang X, Shi J, Wang X, Li H, Miao S, Chen H, He X, Dong L, Lee GR, Zheng J, Liu RJ, Su B, Ye Y, Flavell RA, Yi C, Wu Y, Li HB. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nature Immunology 2022, 23: 1433-1444. PMID: 36138184, DOI: 10.1038/s41590-022-01301-3.Peer-Reviewed Original ResearchConceptsCell expansionKey functional proteinsVivo physiological roleDe novo protein productionCell cycle arrestTranslational controlRNA modificationsMyc proteinFunctional proteinsTranslation efficiencyKey proteinsCell homeostasisProtein productionPhysiological roleProtein synthesisProliferative stateCycle arrestConditional deletionT cell homeostasisNaive T cellsProteinQuiescent stateSpecific subsetT cellsCellsInhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes
Meriin AB, Zaarur N, Bogan JS, Kandror KV. Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes. Scientific Reports 2022, 12: 15640. PMID: 36123369, PMCID: PMC9485115, DOI: 10.1038/s41598-022-19534-5.Peer-Reviewed Original ResearchConceptsInhibitors of RNAGLUT4 translocationProtein synthesisEndocytosis of GLUT4Glucose uptakeRecycling of transferrinGlucose transporter 4Actinomycin DBiosynthesis de novoSignaling proteinsPlasma membraneTransporter 4Intracellular retentionContinuous RNATranslocationRNADe novoAdipocytesVesiclesInhibitorsTBC1D4UptakeEndocytosisGLUT4ExocytosisIdentification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei
Rajan KS, Adler K, Doniger T, Cohen-Chalamish S, Aharon-Hefetz N, Aryal S, Pilpel Y, Tschudi C, Unger R, Michaeli S. Identification and functional implications of pseudouridine RNA modification on small noncoding RNAs in the mammalian pathogen Trypanosoma brucei. Journal Of Biological Chemistry 2022, 298: 102141. PMID: 35714765, PMCID: PMC9283944, DOI: 10.1016/j.jbc.2022.102141.Peer-Reviewed Original ResearchConceptsRNA modificationsLife stagesStage-specific regulationGenome-wide approachesSmall nucleolar RNAsΨ modificationsSmall noncoding RNAsDifferent host environmentsProtein translocationD snoRNAsRRNA modificationVault RNARRNA processingNucleolar RNAsRiboMeth-seqNoncoding RNAsMammalian hostsTrypanosoma bruceiProtein synthesisHost environmentRNAFunctional implicationsTRNABruceiParasitesNascent alt-protein chemoproteomics reveals a pre-60S assembly checkpoint inhibitor
Cao X, Khitun A, Harold CM, Bryant CJ, Zheng SJ, Baserga SJ, Slavoff SA. Nascent alt-protein chemoproteomics reveals a pre-60S assembly checkpoint inhibitor. Nature Chemical Biology 2022, 18: 643-651. PMID: 35393574, PMCID: PMC9423127, DOI: 10.1038/s41589-022-01003-9.Peer-Reviewed Original ResearchConceptsRibosomal subunitDNA damage stressImportant cellular rolesGlobal protein synthesisN-terminal extensionCellular rolesCanonical proteinsHuman cellsProtein synthesisAlternative proteinsCell proliferationChemoproteomicsDamage stressSubunitsProteinAssemblyInhibitorsHypothesis generationMicroproteinsCytoplasmProliferationCellsExportDepletion
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