Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

A mistranslation-prone transcriptome underlying polyglutamine expansion diseases

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

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Girstmair, H. et al. Depletion of cognate charged transfer RNA causes translational frameshifting within the expanded CAG stretch in huntingtin. Cell Rep. 3, 148–159 (2013).

    Article  CAS  Google Scholar 

  2. Nucifora, F. C. et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423–2428 (2001).

    Article  CAS  Google Scholar 

  3. Jiang, H. et al. Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin. Neurobiol. Dis. 23, 543–551 (2006).

    Article  CAS  Google Scholar 

  4. Schaffar, G. et al. Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol. Cell 15, 95–105 (2004).

    Article  CAS  Google Scholar 

  5. Cambridge, S. B. et al. Systems-wide proteomic analysis in mammalian cells reveals conserved, functional protein turnover. J. Proteome Res. 10, 5275–5284 (2011).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Florian Buhr, Prashanth S. Ciryam & Michele Vendruscolo

Authors
  1. Florian Buhr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prashanth S. Ciryam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele Vendruscolo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michele Vendruscolo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Related Links

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

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

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing