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Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon

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Abstract

Regulation of protein synthesis contributes to maintenance of homeostasis and adaptation to environmental changes. mRNA translation is controlled at various levels including initiation, elongation and termination, through post-transcriptional/translational modifications of components of the protein synthesis machinery. Recently, protein and RNA hydroxylation have emerged as important enzymatic modifications of tRNAs, elongation and termination factors, as well as ribosomal proteins. These modifications enable a correct STOP codon recognition, ensuring translational fidelity. Recent studies are starting to show that STOP codon read-through is related to the ability of the cell to cope with different types of stress, such as oxidative and chemical insults, while correlations between defects in hydroxylation of protein synthesis components and STOP codon read-through are beginning to emerge. In this review we will discuss our current knowledge of protein synthesis regulation through hydroxylation of components of the translation machinery, with special focus on STOP codon recognition. We speculate on the possibility that programmed STOP codon read-through, modulated by hydroxylation of components of the protein synthesis machinery, is part of a concerted cellular response to stress.

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Acknowledgments

We wish to thank all members of the Wappner’s lab for discussions and to Peter Ratcliffe for his continuous support. This work was funded by ANPCyT Grants PICT 2014 No. 0649 and PICT 2012 No. 0214. PW is a career investigator of CONICET.

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Authors and Affiliations

  1. Instituto Leloir, Buenos Aires, Argentina

    M. J. Katz, L. Gándara, A. L. De Lella Ezcurra & P. Wappner

  2. Departamento de Fisiología, Biología Molecular, y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina

    P. Wappner

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  1. M. J. Katz
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  2. L. Gándara
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  3. A. L. De Lella Ezcurra
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  4. P. Wappner
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Correspondence to P. Wappner.

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Katz, M.J., Gándara, L., De Lella Ezcurra, A.L. et al. Hydroxylation and translational adaptation to stress: some answers lie beyond the STOP codon. Cell. Mol. Life Sci. 73, 1881–1893 (2016). https://doi.org/10.1007/s00018-016-2160-y

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  • DOI: https://doi.org/10.1007/s00018-016-2160-y

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