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Decoding the Decoding Region: Analysis of Eukaryotic Release Factor (eRF1) Stop Codon-Binding Residues

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Abstract

Peptide synthesis in eukaryotes terminates when eukaryotic release factor 1 (eRF1) binds to an mRNA stop codon and occupies the ribosomal A site. Domain 1 of the eRF1 protein has been implicated in stop codon recognition in a number of experimental studies. In order to further pinpoint the residues of this protein involved in stop codon recognition, we sequenced and compared eRF1 genes from a variety of ciliated protozoan species. We then performed a series of computational analyses to evaluate the conservation, accessibility, and structural environment of each amino acid located in domain 1. With this new dataset and methodology, we were able to identify eight specific amino acid sites important for stop codon recognition and also to propose a set of cooperative paired substitutions that may underlie stop codon reassignment. Our results are more consistent with current experimental data than previously described models.

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Acknowledgments

The authors would like to thank Drs. Wei-Jen Chang and Mona Singh for helpful discussions, Nicholas Stover for critical manuscript reading, and David Prescott, Johannes Hackstein, Mann-Kyoon Shin, and Wei-Jen Chang for gifts of cells or DNA. We thank two anonymous reviewers for their valuable suggestions. This work was supported by NIGMS Grant GM59708 and NSF Award 9875184 to L.F.L.

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Authors and Affiliations

  1. Department of Chemistry, Princeton University, Princeton, NJ, 08544, USA

    Han Liang

  2. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, 08544, USA

    Jonathan Y. Wong, Andre R.O. Cavalcanti & Laura F. Landweber

  3. Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA

    Qing Bao

Authors
  1. Han Liang
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  2. Jonathan Y. Wong
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  3. Qing Bao
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  4. Andre R.O. Cavalcanti
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  5. Laura F. Landweber
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Corresponding author

Correspondence to Laura F. Landweber.

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Han Liang, Jonathan Y. Wong,Contributed equally to this paper

ReviewingEditor: Dr. Niles Lehman

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Liang, H., Wong, J.Y., Bao, Q. et al. Decoding the Decoding Region: Analysis of Eukaryotic Release Factor (eRF1) Stop Codon-Binding Residues. J Mol Evol 60, 337–344 (2005). https://doi.org/10.1007/s00239-004-0211-8

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  • DOI: https://doi.org/10.1007/s00239-004-0211-8

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