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 siteOrganismsTranslocationTranslationMeasuring 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
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
2010
Mutations Disrupting Selenocysteine Formation Cause Progressive Cerebello-Cerebral Atrophy
Agamy O, Zeev B, Lev D, Marcus B, Fine D, Su D, Narkis G, Ofir R, Hoffmann C, Leshinsky-Silver E, Flusser H, Sivan S, Söll D, Lerman-Sagie T, Birk OS. Mutations Disrupting Selenocysteine Formation Cause Progressive Cerebello-Cerebral Atrophy. American Journal Of Human Genetics 2010, 87: 538-544. PMID: 20920667, PMCID: PMC2948803, DOI: 10.1016/j.ajhg.2010.09.007.Peer-Reviewed Original Research
2008
Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality
Nozawa K, O’Donoghue P, Gundllapalli S, Araiso Y, Ishitani R, Umehara T, Söll D, Nureki O. Pyrrolysyl-tRNA synthetase–tRNAPyl structure reveals the molecular basis of orthogonality. Nature 2008, 457: 1163-1167. PMID: 19118381, PMCID: PMC2648862, DOI: 10.1038/nature07611.Peer-Reviewed Original ResearchConceptsAmino acidsMolecular basisLast universal common ancestorUniversal common ancestorUAG stop codonProteinogenic amino acidsCommon ancestorSuppressor tRNAStop codonDesulfitobacterium hafnienseStandard amino acidsTRNADistinct interactionsProteinPyrrolysinePylRSSelenocysteineAncestorCodonMachineryAcidVivoPairsMammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import
Rubio MA, Rinehart JJ, Krett B, Duvezin-Caubet S, Reichert AS, Söll D, Alfonzo JD. Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 9186-9191. PMID: 18587046, PMCID: PMC2453747, DOI: 10.1073/pnas.0804283105.Peer-Reviewed Original ResearchConceptsProtein importMammalian mitochondriaImport systemSubcellular RNA fractionsMitochondrial tRNA genesMitochondrial electrochemical gradientMitochondrial genomeTRNA genesTranscribed tRNAsHuman mitochondriaDefective mitochondriaProtein factorsFiber cellsHeterologous RNATRNACytosolic factorsSufficient ATPRNA fractionHuman cellsHuman diseasesProtein synthesisMitochondriaElectrochemical gradientOligonucleotide primersVitro systemLife without RNase P
Randau L, Schröder I, Söll D. Life without RNase P. Nature 2008, 453: 120-123. PMID: 18451863, DOI: 10.1038/nature06833.Peer-Reviewed Original Research
2007
Features of Aminoacyl‐tRNA Synthesis Unique to Archaea
Polycarpo C, Sheppard K, Randau L, Ambrogelly A, Cardoso A, Fukai S, Herring S, Hohn M, Nakamura Y, Oshikane H, Palioura S, Salazar J, Yuan J, Nureki O, Söll D. Features of Aminoacyl‐tRNA Synthesis Unique to Archaea. 2007, 198-208. DOI: 10.1128/9781555815516.ch9.Peer-Reviewed Original ResearchAminoacyl-tRNA synthetasesAmino acidsCognate tRNA speciesCorrect amino acidDomains of lifeAminoacyl-tRNA synthetaseIntron-exon junctionsCorresponding tRNAsNanoarchaeum equitansMethylated thiolsM. jannaschiiMature tRNATRNA speciesGenomic studiesAncient familyBulge motifCysteine synthesisMethanogenic archaeaArchaeaBiosynthetic routeAa-tRNATRNATwo-step pathwayCys-tRNACysSynthetases
2006
Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrion
Krett B, Rinehart J, Rubio M, Alfonzo J, Söll D. Saccharomyces cerevisiae imports the cytosolic pathway for Gln‐tRNA synthesis into the mitochondrion. The FASEB Journal 2006, 20: a500-a500. DOI: 10.1096/fasebj.20.4.a500-b.Peer-Reviewed Original ResearchTransamidation pathwayMitochondrial translationGln-tRNAOrganellar protein synthesisYeast mitochondrial DNAGlutaminyl-tRNA synthetaseAminoacyl-tRNA synthetasesAminoacyl-tRNA formationImport mechanismMitochondrial localizationMitochondrial DNAProtein biosynthesisMost bacteriaCytoplasmic componentsAlternate functionsCytosolic pathwayProtein synthesisAmino acidsEssential processMitochondriaTRNAPathwayEukaryotesGlnRArchaea
2004
Cys-tRNACys formation and cysteine biosynthesis in methanogenic archaea: two faces of the same problem?
Ambrogelly A, Kamtekar S, Sauerwald A, Ruan B, Tumbula-Hansen D, Kennedy D, Ahel I, Söll D. Cys-tRNACys formation and cysteine biosynthesis in methanogenic archaea: two faces of the same problem? Cellular And Molecular Life Sciences 2004, 61: 2437-2445. PMID: 15526152, DOI: 10.1007/s00018-004-4194-9.Peer-Reviewed Original ResearchConceptsMethanogenic archaeaCysteine biosynthesisCellular translation machineryAminoacyl-tRNA synthesisCanonical cysteinyl-tRNA synthetaseAminoacyl-tRNA synthetasesCysteinyl-tRNA synthetaseRecognizable genesTranslation machineryGenome sequenceArchaeaBiosynthesisEssential componentSynthetasesTRNARibosomesGenesMachineryOrganismsSynthetasePossible linkSequenceFormationThe unusual methanogenic seryl‐tRNA synthetase recognizes tRNASer species from all three kingdoms of life
Bilokapic S, Korencic D, Söll D, Weygand‐Durasevic I. The unusual methanogenic seryl‐tRNA synthetase recognizes tRNASer species from all three kingdoms of life. The FEBS Journal 2004, 271: 694-702. PMID: 14764085, DOI: 10.1111/j.1432-1033.2003.03971.x.Peer-Reviewed Original ResearchMeSH KeywordsAnticodonBase SequenceChromatography, GelDimerizationElectrophoretic Mobility Shift AssayEscherichia coliIsoelectric FocusingMethanococcusMolecular Sequence DataNucleic Acid ConformationProtein BindingRNA, Transfer, Amino AcylRNA, Transfer, SerSerineSerine-tRNA LigaseSubstrate SpecificityTranscription, GeneticYeastsConceptsSeryl-tRNA synthetaseGel mobility shift assaysKingdoms of lifeMobility shift assaysMethanococcus jannaschiiM. maripaludisTRNA recognitionShift assaysTRNARenaturation conditionsGel filtration chromatographyConformation of tRNAComplex formationSpeciesFiltration chromatographySynthetaseDimerizationSerRSsJannaschiiTRNASerIsoacceptorsHomologuesComplementary oligonucleotidesAminoacylationRenaturation
2003
Non-canonical Eukaryotic Glutaminyl- and Glutamyl-tRNA Synthetases Form Mitochondrial Aminoacyl-tRNA in Trypanosoma brucei *
Rinehart J, Horn EK, Wei D, Söll D, Schneider A. Non-canonical Eukaryotic Glutaminyl- and Glutamyl-tRNA Synthetases Form Mitochondrial Aminoacyl-tRNA in Trypanosoma brucei *. Journal Of Biological Chemistry 2003, 279: 1161-1166. PMID: 14563839, DOI: 10.1074/jbc.m310100200.Peer-Reviewed Original ResearchConceptsGlutaminyl-tRNA synthetaseGlutamyl-tRNA synthetaseT. bruceiGln-tRNATrypanosoma bruceiInsect stage T. bruceiT. brucei enzymeRespective gene productsAminoacyl-tRNA synthetasesGlutamyl-tRNA synthetase activitySynthetase activityTransamidation pathwayLeishmania mitochondriaBrucei enzymeMitochondrial tRNAsGlu-tRNAProtein biosynthesisAminoacylation experimentsGene productsRNA interferenceTRNABruceiMitochondriaTotal tRNAGlutaminyl
2001
Post-transcriptional modification in archaeal tRNAs: identities and phylogenetic relations of nucleotides from mesophilic and hyperthermophilic Methanococcales
McCloskey J, Graham D, Zhou S, Crain P, Ibba M, Konisky J, Söll D, Olsen G. Post-transcriptional modification in archaeal tRNAs: identities and phylogenetic relations of nucleotides from mesophilic and hyperthermophilic Methanococcales. Nucleic Acids Research 2001, 29: 4699-4706. PMID: 11713320, PMCID: PMC92529, DOI: 10.1093/nar/29.22.4699.Peer-Reviewed Original ResearchConceptsPost-transcriptional modificationsSmall ribosomal subunit RNA sequencesRibose-methylated nucleosidesClose phylogenetic relationshipArchaeal RNAArchaeal tRNAsPhylogenetic relationshipsMethanococcus jannaschiiMethanococcus maripaludisTransfer RNAPhylogenetic relationsBacterial tRNAsMethanococcus vannieliiPosition 37Methanococcus igneusModification differencesModification patternsTRNAMethanococcus thermolithotrophicusRNA sequencesRNATemperature of growthUnknown structureFamily membersEukaryaThe renaissance of aminoacyl‐tRNA synthesis
Ibba M, Söll D. The renaissance of aminoacyl‐tRNA synthesis. EMBO Reports 2001, 2: 382-387. PMID: 11375928, PMCID: PMC1083889, DOI: 10.1093/embo-reports/kve095.Peer-Reviewed Original ResearchConceptsAminoacyl-tRNA synthesisProtein synthesisRole of tRNAEvolutionary diversityStructural biologyMolecular biologistsUnexpected arrayMolecular biologyNew enzymeDecades of studyAmino acidsEssential processTRNABiologyComplete pictureGenomicsAdaptorBiologistsDiversityEnzymePathwayHigh degreeSynthesisNumerous milestones