Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release

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dc.contributor.authorHoernes, Thomas Philipp
dc.contributor.authorClementi, Nina
dc.contributor.authorJuen, Michael Andreas
dc.contributor.authorShi, Xinying
dc.contributor.authorFaserl, Klaus
dc.contributor.authorWilli, Jessica
dc.contributor.authorGasser, Catherina
dc.contributor.authorKreutz, Christoph
dc.contributor.authorJoseph, Simpson
dc.contributor.authorLindner, Herbert
dc.contributor.authorHüttenhofer, Alexander
dc.contributor.authorErlacher, Matthias D.
dc.date.accessioned2025-04-08T23:19:03Z
dc.date.available2025-04-08T23:19:03Z
dc.date.issued2018
dc.descriptionOpen access article. Creative Commons Attribution-NonCommercial-NoDerivatives license (CC BY-NC-ND) applies
dc.description.abstractTermination of protein synthesis is triggered by the recognition of a stop codon at the ribosomal A site and is mediated by class I release factors (RFs). Whereas in bacteria, RF1 and RF2 promote termination at UAA/UAG and UAA/UGA stop codons, respectively, eukaryotes only depend on one RF (eRF1) to initiate peptide release at all three stop codons. Based on several structural as well as biochemical studies, interactions between mRNA, tRNA, and rRNA have been proposed to be required for stop codon recognition. In this study, the influence of these interactions was investigated by using chemically modified stop codons. Single functional groups within stop codon nucleotides were substituted to weaken or completely eliminate specific interactions between the respective mRNA and RFs. Our findings provide detailed insight into the recognition mode of bacterial and eukaryotic RFs, thereby revealing the chemical groups of nucleotides that define the identity of stop codons and provide the means to discriminate against noncognate stop codons or UGG sense codons.
dc.description.peer-reviewYes
dc.identifier.citationHoernes, T. P., Clementi, N., Juen, M. A., Shi, X., Faserl, K., Willi, J., Gasser, C., Kreutz, C., Joseph, S., Lindner, H., Hüttenhofer, A., & Erlacher, M. D. (2018). Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release. PNAS, 115(3), E382-E389. https://doi.org/10.1073/pnas.1714554115
dc.identifier.urihttps://hdl.handle.net/10133/7028
dc.language.isoen
dc.publisherNational Academy of Sciences
dc.publisher.departmentDepartment of Chemistry & Biochemistry
dc.publisher.facultyArts and Science
dc.publisher.institutionMedical University of Innsbruck
dc.publisher.institutionUniversity of Innsbruck
dc.publisher.institutionUniversity of California
dc.publisher.institutionUniversity of Bern
dc.publisher.institutionUniversity of Lethbridge
dc.publisher.urlhttps://doi.org/10.1073/pnas.1714554115
dc.subjectRibosome
dc.subjectTranslation
dc.subjectPeptide release
dc.subjectRelease factor
dc.subjectmRNA modification
dc.subjectStop codons
dc.titleAtomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release
dc.typeArticle
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