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A mistranslation-prone transcriptome underlying polyglutamine expansion diseases

Nature Reviews Molecular Cell Biology volume 22, pages 583–584 (2021)Cite this article

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We propose a mechanism underlying polyglutamine (polyQ) repeat expansion diseases, in which the translation of expanded CAG codon repeats leads to translation stress. The stress is generated by depletion of the cognate glutaminyl-tRNA pool, which could cause ribosome frameshifting and lead to mistranslation of transcripts with specific characteristics.

A balanced composition of cellular proteins is essential for maintaining cell homeostasis and function. Advances have been made in elucidating the links between human disease and failures in the folding, trafficking and degradation of proteins. Less is known, however, about the causes and consequences of aberrant mRNA translation.

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Authors and Affiliations

  1. Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, UK

    Florian Buhr, Prashanth S. Ciryam & Michele Vendruscolo

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  1. Florian Buhr
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  2. Prashanth S. Ciryam
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  3. Michele Vendruscolo
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Correspondence to Michele Vendruscolo.

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The authors declare no competing interests.

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PolyQ 2.0 database: https://lightning.erc.monash.edu/

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Buhr, F., Ciryam, P.S. & Vendruscolo, M. A mistranslation-prone transcriptome underlying polyglutamine expansion diseases. Nat Rev Mol Cell Biol 22, 583–584 (2021). https://doi.org/10.1038/s41580-021-00368-4

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  • DOI: https://doi.org/10.1038/s41580-021-00368-4

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