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Antigenic peptides

Reviving nuclear translation

Nature Chemical Biology volume 9, pages 759–760 (2013)Cite this article

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Noncanonical translation of prespliced mRNA provides physiological meaning to nuclear translation in generating antigenic peptide substrates for the endogenous major histocompatibility complex class I pathway.

The concept of nuclear translation, described for the first time by Allfrey et al.5 in the early 1950s, has been heavily debated, though with few converts in the intervening years. Despite some favorable evidence for nuclear translation, the lack of controls and use of impure nuclei or damaged cells meant that this evidence had little influence on the prevailing view of the cytoplasm being the scene of restricted translation. Recently, however, the concept of nuclear translation was revived in a study by David et al.6, which demonstrated substantial nucleolar enriched translation in intact cells by means of ribopuromycylation, creating stably associated complexes of ribosomes with puromycylated nascent chains. Interestingly, this study also showed that nuclear translation was specifically inhibited upon influenza infection. One explanation for this result is that nuclear translation functions in the quality control of mRNA transcripts by processes such as nonsense-mediated decay (NMD), a surveillance pathway that reduces errors in gene expression by eliminating mRNA transcripts containing premature stop codons (PTCs), which generate defective ribosomal products as a consequence. Another attractive hypothesis is that certain viruses have evolved mechanisms to prevent antigenic peptide formation during the pioneer round of mRNA translation1.

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Figure 1: Model for antigenic MHC class I peptide substrate generation.

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Authors and Affiliations

  1. Petra Van Damme is at the Department of Medical Protein Research, and the Department of Biochemistry, VIB, Ghent, Belgium, Ghent University, Ghent, Belgium.,

    Petra Van Damme

  2. Department of Mathematical Modeling, Gerben Menschaert is at the Laboratory for Bioinformatics and Computational Genomics, Statistics and Bioinformatics, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.,

    Gerben Menschaert

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  1. Petra Van Damme
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  2. Gerben Menschaert
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Correspondence to Petra Van Damme.

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Van Damme, P., Menschaert, G. Reviving nuclear translation. Nat Chem Biol 9, 759–760 (2013). https://doi.org/10.1038/nchembio.1394

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