2025
Mitochondrial tRNA fragment, mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB), in breast cancer and its potential clinical implications
Wang J, Katsaros D, Wang Z, Ma L, Casetta E, Fei P, Denti P, Grimaudo I, Chen S, Deng Y, Yu H. Mitochondrial tRNA fragment, mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB), in breast cancer and its potential clinical implications. Breast Cancer Research And Treatment 2025, 211: 675-685. PMID: 40102335, DOI: 10.1007/s10549-025-07682-x.Peer-Reviewed Original ResearchConceptsBreast tumorsInvolvement of tRNARegulation of cell phenotypeSuppress breast cancer progressionSmall non-coding RNAsIn silico analysisOncogenic transcription factorHormone receptor statusCox proportional hazards regressionMitochondrial tRNAsBreast cancer progressionCleaves tRNATRNA fragmentsProportional hazards regressionRNase 4Non-coding RNAsPotential clinical implicationsResting mast cellsTranscription factorsSilico analysisReceptor statusTumor immunityQuantitative RT-PCRTRNATumor gradeThioesters Support Efficient Protein Biosynthesis by the Ribosome
Kent A, Robins J, Knudson I, Vance J, Solivan A, Hamlish N, Fitzgerald K, Schepartz A, Miller S, Cate J. Thioesters Support Efficient Protein Biosynthesis by the Ribosome. ACS Central Science 2025, 11: 404-412. PMID: 40161951, PMCID: PMC11950863, DOI: 10.1021/acscentsci.4c01698.Peer-Reviewed Original ResearchProtein biosynthesisIn vitro translation reactionsCCA-adding enzymeEfficient protein biosynthesisAminoacyl-tRNA synthetasesTranslation machineryTranslation reactionsThioester intermediateRibosomeBiochemical reactionsEffective substrateThioesterBiosynthesisA-amino acidsTruncated tRNAsTRNATRNAsPeptide synthesisPolymer synthesisOxo-esterPrebiotic peptide synthesisSynthetaseXyloseExchange reactionFlexizymes
2024
Quantifying constraint in the human mitochondrial genome
Lake N, Ma K, Liu W, Battle S, Laricchia K, Tiao G, Puiu D, Ng K, Cohen J, Compton A, Cowie S, Christodoulou J, Thorburn D, Zhao H, Arking D, Sunyaev S, Lek M. Quantifying constraint in the human mitochondrial genome. Nature 2024, 635: 390-397. PMID: 39415008, PMCID: PMC11646341, DOI: 10.1038/s41586-024-08048-x.Peer-Reviewed Original ResearchMitochondrial genomeDeleterious variationMtDNA mutator modelHuman mitochondrial genomeGenome Aggregation DatabaseMtDNA variationMtDNA variantsMitochondrial DNANoncoding regionsMitochondrial proteinsRRNA geneGenetic variationMtDNAThree-dimensional structureMutation modelPathogenic variationDisease relevanceAggregation DatabaseGenomeLarge-scale population datasetRRNAConstrained sitesGenesTRNAPopulation datasetsRluA 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 elementsSynthaseRNASequenceEukaryotesMechanistic Basis for the Translation Inhibition of Cutibacterium acnes by Clindamycin
Lomakin I, Devarkar S, Grada A, Bunick C. Mechanistic Basis for the Translation Inhibition of Cutibacterium acnes by Clindamycin. Journal Of Investigative Dermatology 2024, 144: 2553-2561.e3. PMID: 39122144, DOI: 10.1016/j.jid.2024.07.013.Peer-Reviewed Original ResearchNetwork of water-mediated interactionsCutibacterium acnesPeptide bond formationNascent peptideWater-mediated interactionsTranslational inhibitionAntibiotic resistanceCryogenic electron microscopyA-resolutionMechanistic basesAntibiotic-based therapiesRRNAAminoacyl groupRibosomeAcne pathogenesisAcne therapyAntibiotic stewardshipClindamycinIncreased resistanceAcne vulgarisClinical targetsAcneAntibioticsPeptideTRNA
2023
Rational design of the genetic code expansion toolkit for in vivo encoding of D-amino acids
Jiang H, Weng J, Wang Y, Tsou J, Chen P, Ko A, Söll D, Tsai M, Wang Y. Rational design of the genetic code expansion toolkit for in vivo encoding of D-amino acids. Frontiers In Genetics 2023, 14: 1277489. PMID: 37904728, PMCID: PMC10613524, DOI: 10.3389/fgene.2023.1277489.Peer-Reviewed Original ResearchUnique biophysical propertiesTree of lifeAmino acidsSuperfolder green fluorescent proteinGreen fluorescent proteinSubstrate polyspecificityTranslational machinerySynthetic biologistsSmall proteinsFluorescent proteinPhysiological roleRibosomal synthesisProteinBiophysical propertiesKinetic assaysHuman heavy chain ferritinHeavy-chain ferritinPylRSTRNAMutantsAminoacylationPeptidesBiologistsPhysiochemical propertiesMachineryRecoding UAG to selenocysteine in Saccharomyces cerevisiae
Hoffman K, Chung C, Mukai T, Krahn N, Jiang H, Balasuriya N, O'Donoghue P, Söll D. Recoding UAG to selenocysteine in Saccharomyces cerevisiae. RNA 2023, 29: 1400-1410. PMID: 37279998, PMCID: PMC10573291, DOI: 10.1261/rna.079658.123.Peer-Reviewed Original ResearchConceptsSelenoprotein productionYeast expression systemSeryl-tRNA synthetaseSite-specific incorporationEukaryotic relativesKingdom FungiSelenocysteine synthaseSelenophosphate synthetaseBiosynthesis pathwayEukaryotic selenoproteinsMetabolic engineeringBiosynthetic pathwayPathway componentsExpression systemReductase enzymeTRNASaccharomycesYeastTranslation componentsSpecific sitesFacile productionUnique chemicalSynthetasePathwayFirst demonstration
2022
Ancestral archaea expanded the genetic code with pyrrolysine
Guo LT, Amikura K, Jiang HK, Mukai T, Fu X, Wang YS, O’Donoghue P, Söll D, Tharp JM. Ancestral archaea expanded the genetic code with pyrrolysine. Journal Of Biological Chemistry 2022, 298: 102521. PMID: 36152750, PMCID: PMC9630628, DOI: 10.1016/j.jbc.2022.102521.Peer-Reviewed Original ResearchConceptsAminoacylation efficiencyGenetic code expansionDomains of lifePyrrolysyl-tRNA synthetaseTRNA-binding domainFull-length enzymeNoncanonical amino acidsAmino acid substratesMolecular phylogenyDiverse archaeaCoevolutionary historyTRNA sequencesGenetic codeCode expansionDiscriminator basesMethanogenic archaeaMethanosarcina mazeiPylRSSubstrate spectrumTRNAArchaeaMultiple organismsLiving cellsAcid substratesAmino acidsUncovering translation roadblocks during the development of a synthetic tRNA
Prabhakar A, Krahn N, Zhang J, Vargas-Rodriguez O, Krupkin M, Fu Z, Acosta-Reyes FJ, Ge X, Choi J, Crnković A, Ehrenberg M, Puglisi EV, Söll D, Puglisi J. Uncovering translation roadblocks during the development of a synthetic tRNA. Nucleic Acids Research 2022, 50: 10201-10211. PMID: 35882385, PMCID: PMC9561287, DOI: 10.1093/nar/gkac576.Peer-Reviewed Original ResearchConceptsOrthogonal translation systemGenetic code expansionCode expansionTertiary interactionsNon-canonical amino acidsAminoacyl-tRNA substratesDomains of lifeAminoacyl-tRNA synthetaseTranslation systemSingle nucleotide mutationsSingle-molecule fluorescenceDistinct tRNAsNon-canonical structuresSelenocysteine insertionRibosomal translationTRNARibosomesSynthetic tRNANucleotide mutationsAmino acidsSame organismP siteOrganismsTranslocationTranslationIdentification 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 implicationsTRNABruceiParasitesTranscriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA
Draycott AS, Schaening-Burgos C, Rojas-Duran MF, Wilson L, Schärfen L, Neugebauer KM, Nachtergaele S, Gilbert WV. Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA. PLOS Biology 2022, 20: e3001622. PMID: 35609439, PMCID: PMC9129914, DOI: 10.1371/journal.pbio.3001622.Peer-Reviewed Original ResearchConceptsTranscriptome-wide mappingSmall nucleolar RNAsFunctional RNA structuresSingle-nucleotide resolutionStem-loop regionEukaryotic ribosomesNucleolar RNAsPre-mRNARNA structureRNA targetsDihydrouridine synthaseHuman diseasesMRNARNANovel classFunctional componentsSplicingTRNARibosomesYeastDependent changesLandscapeOrganismsDihydrouridineSequencingMeasuring the tolerance of the genetic code to altered codon size
DeBenedictis EA, Söll D, Esvelt KM. Measuring the tolerance of the genetic code to altered codon size. ELife 2022, 11: e76941. PMID: 35293861, PMCID: PMC9094753, DOI: 10.7554/elife.76941.Peer-Reviewed Original ResearchConceptsFour-base codonsGenetic codeTRNA mutationsAminoacyl-tRNA synthetasesQuadruplet codonsSingle amino acidCodon translationTriplet codonsTRNA synthetasesSynthetic biologistsCodonTRNAAmino acidsChemical alphabetsMutationsMass spectrometrySynthetasesAnticodonToleranceSynthetic systemsBiologistsTranslationEscherichiaNascent
2020
Initiation of Protein Synthesis with Non‐Canonical Amino Acids In Vivo
Tharp J, Ad O, Amikura K, Ward F, Garcia E, Cate J, Schepartz A, Söll D. Initiation of Protein Synthesis with Non‐Canonical Amino Acids In Vivo. Angewandte Chemie 2020, 132: 3146-3150. DOI: 10.1002/ange.201914671.Peer-Reviewed Original ResearchNon-canonical amino acidsDistinct non-canonical amino acidsE. coli translational machineryAmino acidsNon-canonical initiationTRNA fMetTranslational machineryInitiator tRNASynthetic biologyE. coli strainsProtein synthesisDiverse sidechainsColi strainsFMetRemarkable versatilityVivoInitial stepSecond positionGenomeTyrRSTRNARedundant copiesMachineryBiologyPolypeptide
2016
An Engineered Rare Codon Device for Optimization of Metabolic Pathways
Wang Y, Li C, Khan M, Wang Y, Ruan Y, Zhao B, Zhang B, Ma X, Zhang K, Zhao X, Ye G, Guo X, Feng G, He L, Ma G. An Engineered Rare Codon Device for Optimization of Metabolic Pathways. Scientific Reports 2016, 6: 20608. PMID: 26852704, PMCID: PMC4745014, DOI: 10.1038/srep20608.Peer-Reviewed Original ResearchConceptsRare codonsCognate tRNAMetabolic pathwaysExpression levelsProtein expressionTarget protein expressionAspartyl-tRNA synthetaseCodons AGGReporter geneRelevant enzymesCopy numberEscherichia coliCodonFatty acid yieldGenesSteady-state kineticsE. coliTRNAPathwayExpressionColiIntermediate levelsTwo-fold increaseSynthetaseAcid yield
2014
The RtcB RNA ligase is an essential component of the metazoan unfolded protein response
Kosmaczewski SG, Edwards TJ, Han SM, Eckwahl MJ, Meyer BI, Peach S, Hesselberth JR, Wolin SL, Hammarlund M. The RtcB RNA ligase is an essential component of the metazoan unfolded protein response. EMBO Reports 2014, 15: 1278-1285. PMID: 25366321, PMCID: PMC4264930, DOI: 10.15252/embr.201439531.Peer-Reviewed Original ResearchConceptsUnfolded protein responseProtein responseRNA ligationIRE-1 branchesMultiple essential processesRNA ligase RtcBXBP-1 mRNACaenorhabditis elegansRNA functionRtcBMRNA fragmentsTarget RNARNA sequencesXBP-1RNA ligaseTRNAEssential processEssential componentMaturationElegansLifespanMutantsLigaseVivo modelXBP1Bacterial noncoding Y RNAs are widespread and mimic tRNAs
Chen X, Sim S, Wurtmann EJ, Feke A, Wolin SL. Bacterial noncoding Y RNAs are widespread and mimic tRNAs. RNA 2014, 20: 1715-1724. PMID: 25232022, PMCID: PMC4201824, DOI: 10.1261/rna.047241.114.Peer-Reviewed Original ResearchConceptsY RNAsStructured RNA degradationRing-shaped proteinNoncoding Y RNAsBacterial physiologyAnimal cellsNucleotide modificationsDeinococcus radioduransPhage speciesRNA degradationTRNARo60 autoantigenRNAOrthologsNcRNAsSpeciesBacteriaExoribonucleaseRNAsRadioduransProteinRo60EnzymePhysiologyPhosphorylaseCLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration
Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E, Coufal NG, Silhavy JL, Xue Y, Kayserili H, Yasuno K, Rosti RO, Abdellateef M, Caglar C, Kasher PR, Cazemier JL, Weterman MA, Cantagrel V, Cai N, Zweier C, Altunoglu U, Satkin NB, Aktar F, Tuysuz B, Yalcinkaya C, Caksen H, Bilguvar K, Fu XD, Trotta CR, Gabriel S, Reis A, Gunel M, Baas F, Gleeson JG. CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration. Cell 2014, 157: 651-663. PMID: 24766810, PMCID: PMC4128918, DOI: 10.1016/j.cell.2014.03.049.Peer-Reviewed Original ResearchConceptsPre-tRNA cleavagePolyadenylation factor INull zebrafishTRNA splicingMultifunctional kinaseTRNA maturationMature tRNAEndonuclease complexMutant proteinsKinase activityOxidative stress-induced reductionInduced neuronsNeuronal developmentCell survivalIndependent pedigreesPatient cellsConsanguineous familyCerebellar neurodegenerationTRNACerebellar developmentNeurodegenerative diseasesMaturationNeurodegenerationStress-induced reductionFactor I
2013
Back Cover: Rewiring Translation for Elongation Factor Tu‐Dependent Selenocysteine Incorporation (Angew. Chem. Int. Ed. 5/2013)
Aldag C, Bröcker M, Hohn M, Prat L, Hammond G, Plummer A, Söll D. Back Cover: Rewiring Translation for Elongation Factor Tu‐Dependent Selenocysteine Incorporation (Angew. Chem. Int. Ed. 5/2013). Angewandte Chemie International Edition 2013, 52: 1596-1596. DOI: 10.1002/anie.201300063.Peer-Reviewed Original Research
2012
Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment
Ling J, Peterson KM, Simonović I, Cho C, Söll D, Simonović M. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 3281-3286. PMID: 22343532, PMCID: PMC3295322, DOI: 10.1073/pnas.1200109109.Peer-Reviewed Original ResearchMeSH KeywordsAeropyrumAmino Acid SequenceAnticodonCatalytic DomainCodonCrystallography, X-RayEscherichia coliEvolution, MolecularLeucineMitochondriaModels, MolecularMolecular Sequence DataProtein ConformationProtein Structure, TertiaryRNA EditingRNA, Transfer, Amino AcylSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence AlignmentSpecies SpecificityStaphylococcus aureusSubstrate SpecificityThreonineThreonine-tRNA LigaseConceptsThreonyl-tRNA synthetaseAnticodon loopAnticodon sequenceEscherichia coli ThrRSSet of tRNAsDistinct recognition mechanismsAnticodon-binding domainAminoacyl-tRNA synthetasesCUN codonsDetailed structural comparisonCodon reassignmentYeast mitochondriaGenetic codeTRNA isoacceptorsSaccharomyces cerevisiaeIsoacceptor tRNAsEditing domainTRNAMST1Anticodon tripletStructural comparisonNatural tRNAAmino acidsDistinct mechanismsRecognition mechanism
2011
tRNA import into mitochondria: many organisms but not so many mechanisms
Alfonzo J, Randau L, Söll D. tRNA import into mitochondria: many organisms but not so many mechanisms. The FASEB Journal 2011, 25: 311.3-311.3. DOI: 10.1096/fasebj.25.1_supplement.311.3.Peer-Reviewed Original ResearchTRNA importMitochondrial genomeMammalian mitochondriaImport of tRNAsMajority of eukaryotesMitochondrial tRNA mutationsProtein importImport pathwayTRNA genesImport systemAdditional tRNAsTRNA mutationsTRNACellular ATPMitochondriaEukaryotesOrganismsGenomeRat liver mitochondriaLiver mitochondriaImportInnate abilityGenesTrypanosomesCytoplasm
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