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

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Date
2018
Authors
Hoernes, Thomas Philipp
Clementi, Nina
Juen, Michael Andreas
Shi, Xinying
Faserl, Klaus
Willi, Jessica
Gasser, Catherina
Kreutz, Christoph
Joseph, Simpson
Lindner, Herbert
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Journal ISSN
Volume Title
Publisher
National Academy of Sciences
Abstract
Termination 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.
Description
Open access article. Creative Commons Attribution-NonCommercial-NoDerivatives license (CC BY-NC-ND) applies
Keywords
Ribosome , Translation , Peptide release , Release factor , mRNA modification , Stop codons
Citation
Hoernes, 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
URI
https://hdl.handle.net/10133/7028
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Willi, Jessica