2025
Engineering a genomically recoded organism with one stop codon
Grome M, Nguyen M, Moonan D, Mohler K, Gurara K, Wang S, Hemez C, Stenton B, Cao Y, Radford F, Kornaj M, Patel J, Prome M, Rogulina S, Sozanski D, Tordoff J, Rinehart J, Isaacs F. Engineering a genomically recoded organism with one stop codon. Nature 2025, 639: 512-521. PMID: 39910296, PMCID: PMC11903333, DOI: 10.1038/s41586-024-08501-x.Peer-Reviewed Original Research
2023
Mistranslation of the genetic code by a new family of bacterial transfer RNAs
Schuntermann D, Fischer J, Bile J, Gaier S, Shelley B, Awawdeh A, Jahn M, Hoffman K, Westhof E, Söll D, Clarke C, Vargas-Rodriguez O. Mistranslation of the genetic code by a new family of bacterial transfer RNAs. Journal Of Biological Chemistry 2023, 299: 104852. PMID: 37224963, PMCID: PMC10404621, DOI: 10.1016/j.jbc.2023.104852.Peer-Reviewed Original ResearchConceptsTransfer RNAsAmino acidsBacterial transfer RNAsUnfavorable environmental conditionsProlyl-tRNA synthetaseWrong amino acidPoor substrate specificitySubstrate discriminationGrowth defectTransfer RNAGenetic codePosttranslational modificationsProtein reporterTranslation factorsEnvironmental stressFunctional proteinsSubstrate specificityThreonine codonGenetic informationDistinct isoformsPro mutationAntibiotic carbenicillinEscherichia coliNovel familyEnvironmental conditions
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 acidsThe tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism
Zhang H, Gong X, Zhao Q, Mukai T, Vargas-Rodriguez O, Zhang H, Zhang Y, Wassel P, Amikura K, Maupin-Furlow J, Ren Y, Xu X, Wolf YI, Makarova KS, Koonin EV, Shen Y, Söll D, Fu X. The tRNA discriminator base defines the mutual orthogonality of two distinct pyrrolysyl-tRNA synthetase/tRNAPyl pairs in the same organism. Nucleic Acids Research 2022, 50: gkac271-. PMID: 35466371, PMCID: PMC9071458, DOI: 10.1093/nar/gkac271.Peer-Reviewed Original ResearchConceptsGenetic code expansionCode expansionDistinct non-canonical amino acidsOrthogonal aminoacyl-tRNA synthetase/tRNA pairsAminoacyl-tRNA synthetase/tRNA pairsPyrrolysyl-tRNA synthetase/Halophilic archaeon Haloferax volcaniiAdditional coding capacityDistinct noncanonical amino acidsNon-canonical amino acidsArchaeon Haloferax volcaniiDiscriminator baseAmino acidsPyrrolysyl-tRNA synthetaseNoncanonical amino acidsSite-specific incorporationMotif 2 loopSingle base changeDistinct tRNAsTRNA pairsHaloferax volcaniiUAA codonGenetic codeDiscriminator basesTRNA structureMeasuring 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 ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAnticodonCodonEscherichia coliGenetic CodeProtein BiosynthesisRNA, TransferConceptsFour-base codonsGenetic codeTRNA mutationsAminoacyl-tRNA synthetasesQuadruplet codonsSingle amino acidCodon translationTriplet codonsTRNA synthetasesSynthetic biologistsCodonTRNAAmino acidsChemical alphabetsMutationsMass spectrometrySynthetasesAnticodonToleranceSynthetic systemsBiologistsTranslationEscherichiaNascent
2020
Protein-coding changes preceded cis-regulatory gains in a newly evolved transcription circuit
Britton C, Sorrells T, Johnson A. Protein-coding changes preceded cis-regulatory gains in a newly evolved transcription circuit. Science 2020, 367: 96-100. PMID: 31896718, PMCID: PMC8284397, DOI: 10.1126/science.aax5217.Peer-Reviewed Original Research
2015
The PsychENCODE project
Akbarian S, Liu C, Knowles JA, Vaccarino FM, Farnham PJ, Crawford GE, Jaffe AE, Pinto D, Dracheva S, Geschwind DH, Mill J, Nairn AC, Abyzov A, Pochareddy S, Prabhakar S, Weissman S, Sullivan PF, State MW, Weng Z, Peters MA, White KP, Gerstein MB, Amiri A, Armoskus C, Ashley-Koch AE, Bae T, Beckel-Mitchener A, Berman BP, Coetzee GA, Coppola G, Francoeur N, Fromer M, Gao R, Grennan K, Herstein J, Kavanagh DH, Ivanov NA, Jiang Y, Kitchen RR, Kozlenkov A, Kundakovic M, Li M, Li Z, Liu S, Mangravite LM, Mattei E, Markenscoff-Papadimitriou E, Navarro FC, North N, Omberg L, Panchision D, Parikshak N, Poschmann J, Price AJ, Purcaro M, Reddy TE, Roussos P, Schreiner S, Scuderi S, Sebra R, Shibata M, Shieh AW, Skarica M, Sun W, Swarup V, Thomas A, Tsuji J, van Bakel H, Wang D, Wang Y, Wang K, Werling DM, Willsey AJ, Witt H, Won H, Wong CC, Wray GA, Wu EY, Xu X, Yao L, Senthil G, Lehner T, Sklar P, Sestan N. The PsychENCODE project. Nature Neuroscience 2015, 18: 1707-1712. PMID: 26605881, PMCID: PMC4675669, DOI: 10.1038/nn.4156.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainChromosome MappingEpigenesis, GeneticGenetic CodeHumansMental DisordersTranscriptomeOvercoming Challenges in Engineering the Genetic Code
Lajoie M, Söll D, Church G. Overcoming Challenges in Engineering the Genetic Code. Journal Of Molecular Biology 2015, 428: 1004-1021. PMID: 26348789, PMCID: PMC4779434, DOI: 10.1016/j.jmb.2015.09.003.Peer-Reviewed Original ResearchTissue-based map of the human proteome
Uhlén M, Fagerberg L, Hallström B, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edlund K, Lundberg E, Navani S, Szigyarto C, Odeberg J, Djureinovic D, Takanen J, Hober S, Alm T, Edqvist P, Berling H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk J, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F. Tissue-based map of the human proteome. Science 2015, 347: 1260419. PMID: 25613900, DOI: 10.1126/science.1260419.Peer-Reviewed Original ResearchConceptsPutative protein-coding genesHuman tissue proteomesProtein-coding genesInteractive web-based databaseIntegrated omics approachDifferent tissuesGlobal expression patternsSingle-cell levelMembrane proteomeProteome variationDruggable proteomeOmics approachesHuman proteomeHuman secretomeMolecular detailsIndividual proteinsQuantitative transcriptomicsCancer proteomeTissue proteomeProteomeExpression patternsHuman biologyMetabolic functionsTissue microarray-based immunohistochemistryMajor tissues
2014
Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells
Carlile TM, Rojas-Duran MF, Zinshteyn B, Shin H, Bartoli KM, Gilbert WV. Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells. Nature 2014, 515: 143-146. PMID: 25192136, PMCID: PMC4224642, DOI: 10.1038/nature13802.Peer-Reviewed Original Research
2013
UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota
Campbell JH, O’Donoghue P, Campbell AG, Schwientek P, Sczyrba A, Woyke T, Söll D, Podar M. UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 5540-5545. PMID: 23509275, PMCID: PMC3619370, DOI: 10.1073/pnas.1303090110.Peer-Reviewed Original ResearchConceptsFrame TGA codonTGA codonGlycine codonHuman microbiotaSingle-cell genome sequencesSmall subunit rRNA sequencesComparative genomic analysisHorizontal gene transferUnique genetic codeGlycyl-tRNA synthetaseHuman Microbiome Project dataStrain-specific variationMost genesSuch taxaBisphosphate carboxylaseGenome sequenceGenetic codeGenomic analysisStriking diversityRRNA sequencesΒ-galactosidase activityGlycine residueStop codonCodonLacZ gene
2011
Expanding the Genetic Code of Escherichia coli with Phosphoserine
Park HS, Hohn MJ, Umehara T, Guo LT, Osborne EM, Benner J, Noren CJ, Rinehart J, Söll D. Expanding the Genetic Code of Escherichia coli with Phosphoserine. Science 2011, 333: 1151-1154. PMID: 21868676, PMCID: PMC5547737, DOI: 10.1126/science.1207203.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acyl-tRNA SynthetasesAnticodonChloramphenicolChloramphenicol O-AcetyltransferaseCodon, TerminatorDrug Resistance, BacterialEscherichia coliGenetic CodeGenetic EngineeringHumansMAP Kinase Kinase 1Peptide Elongation Factor TuPhosphoserineProtein EngineeringProtein Modification, TranslationalRecombinant Fusion ProteinsRNA, BacterialRNA, Transfer, Amino Acid-SpecificRNA, Transfer, Amino AcylRNA, Transfer, CysTransfer RNA AminoacylationConceptsGenetic codeEF-TuMitogen-activated ERKQuality control functionTransfer RNAProtein engineeringEscherichia coli strainsKinase 1Phosphoamino acidsMolecular biologyEscherichia coliO-phosphoserineColi strainsGeneral utilityDisease researchCanonical positionPhosphoproteomePhosphoserineRNABiologyERKProteinSynthetaseColiResidues
2008
Quality control despite mistranslation caused by an ambiguous genetic code
Ruan B, Palioura S, Sabina J, Marvin-Guy L, Kochhar S, LaRossa RA, Söll D. Quality control despite mistranslation caused by an ambiguous genetic code. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 16502-16507. PMID: 18946032, PMCID: PMC2575449, DOI: 10.1073/pnas.0809179105.Peer-Reviewed Original ResearchConceptsGenetic codeAa-tRNAWild-type proteinAminoacyl-tRNA synthetasesInactive mutant proteinsHeat shock responseE. coliMutant proteinsReporter proteinMissense suppressionFunctional proteinsCognate tRNASelective pressureAminoacyl-tRNAActive enzymeShock responseProtein synthesisNative conformationEnergetic costAmino acidsMissense mutationsProteinBiochemical evidenceCorrect pairingProtein quality
2002
Molecular biology: A brief overview
Gahtan V, Olson ET, Sumpio BE. Molecular biology: A brief overview. Journal Of Vascular Surgery 2002, 35: 563-568. PMID: 11877707, DOI: 10.1067/mva.2002.120039.Peer-Reviewed Original Research
2001
Protein synthesis: Twenty three amino acids and counting
Ibba M, Stathopoulos C, Söll D. Protein synthesis: Twenty three amino acids and counting. Current Biology 2001, 11: r563-r565. PMID: 11509255, DOI: 10.1016/s0960-9822(01)00344-x.Peer-Reviewed Original Research
2000
Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process
Woese C, Olsen G, Ibba M, Söll D. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process. Microbiology And Molecular Biology Reviews 2000, 64: 202-236. PMID: 10704480, PMCID: PMC98992, DOI: 10.1128/mmbr.64.1.202-236.2000.Peer-Reviewed Original ResearchMeSH KeywordsAmino AcidsAmino Acyl-tRNA SynthetasesArchaeaChlorobiEvolution, MolecularGenetic CodePhylogenySpirochaetaThermusConceptsAminoacyl-tRNA synthetasesIndividual aminoacyl-tRNA synthetasesEvolutionary processesAAR geneEvolutionary relationshipsPhylogenetic treeGenetic codeUniversal phylogenetic treeDistant evolutionary pastOrganismal phylogenyOrganismal domainsCodon assignmentsTaxonomic distributionEvolutionary pastHorizontal transferEvolutionary profilesGenetic materialIndividual enzymesEvolutionary perspectiveSynthetasesGenesEnzymeBacteriaModern counterpartsTrees
1999
Archaeal aminoacyl-tRNA synthesis: unique determinants of a universal genetic code?
Ibba M, Curnow A, Bono J, Rosa P, Woese C, Söll D. Archaeal aminoacyl-tRNA synthesis: unique determinants of a universal genetic code? Biological Bulletin 1999, 196: 335-6; discussion 336-7. PMID: 10390832, DOI: 10.2307/1542964.Peer-Reviewed Original Research
1995
Divergence of glutamate and glutamine aminoacylation pathways: Providing the evolutionary rationale for mischarging
Rogers K, Söll D. Divergence of glutamate and glutamine aminoacylation pathways: Providing the evolutionary rationale for mischarging. Journal Of Molecular Evolution 1995, 40: 476-481. PMID: 7783222, DOI: 10.1007/bf00166615.Peer-Reviewed Original ResearchConceptsGlutaminyl-tRNA synthetaseGlutamine tRNAEukaryotic organismsProkaryotic organismsGln-tRNAGlnHorizontal gene transfer eventsGene transfer eventsGlutaminyl-tRNA synthetasesGram-negative eubacteriaGlutamyl-tRNA synthetaseAminoacyl-tRNA synthetasesAminoacyl-tRNA synthetaseFamily of enzymesEukaryotic organellesPool of glutamateAminoacyl-tRNATRNADifferent cellular mechanismsEvolutionary rationaleProtein synthesisOrganismsAmino acidsTransfer eventsCellular mechanismsSynthetase
1994
Non-equilibrium dynamics as an indispensable characteristic of a healthy biological system
Peng C, Buldyrev S, Hausdorff J, Havlin S, Mietus J, Simons M, Stanley H, Goldberger A. Non-equilibrium dynamics as an indispensable characteristic of a healthy biological system. Integrative Psychological And Behavioral Science 1994, 29: 283-293. PMID: 7811648, DOI: 10.1007/bf02691332.Peer-Reviewed Original Research
1990
The accuracy of aminoacylation — ensuring the fidelity of the genetic code
Söll D. The accuracy of aminoacylation — ensuring the fidelity of the genetic code. Cellular And Molecular Life Sciences 1990, 46: 1089-1096. PMID: 2253707, DOI: 10.1007/bf01936918.Peer-Reviewed Original ResearchConceptsAccuracy of aminoacylationTransfer RNA speciesAminoacyl-tRNA synthetasesMessenger RNA codonRNA speciesProtein biosynthesisGenetic codeProtein interactionsParticular tRNATRNACorrect attachmentBiophysical techniquesRNA codonsAmino acidsSynthetasesSpecific recognitionProper interactionAnticodonBiosynthesisCodonAminoacylationNucleotidesSpeciesEnzymeIdentity element
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