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.

  • Research Briefing
  • Published:

Dysregulation of RNA methylation contributes to neurodegeneration

We found reduced N6-methyladenosine (m6A) RNA modification in neurons differentiated from induced pluripotent stem cells from patients with amyotrophic lateral sclerosis or frontotemporal dementia caused by C9orf72 repeat expansion. This reduction disturbs global gene expression and exacerbates neurodegeneration. Strategies to restore the m6A level hold great promise as therapeutic approaches.

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

Access options

Buy this article

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

Fig. 1: m6A hypomethylation contributes to neuron dysfunction and degeneration.

References

  1. Nussbacher, J. K., Tabet, R., Yeo, G. W. & Lagier-Tourenne, C. Disruption of RNA metabolism in neurological diseases andemerging therapeutic interventions. Neuron 102, 294–320 (2019). A review of neurological diseases with RNA metabolism dysregulation and the potential mechanisms.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R. & Gitler, A. D. ALS genetics: gains, losses, and implications for future therapies. Neuron 108, 822–842 (2020). A review of ALS genetics and disease mechanisms.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Balendra, R. & Isaacs, A. M. C9orf72-mediated ALS and FTD: multiple pathways to disease. Nat. Rev. Neurol. 14, 544–558 (2018). A review of pathogenetic mechanisms of C9orf72-mediated ALS and FTD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Roundtree, I. A., Evans, M. E., Pan, T. & He, C. Dynamic RNA modifications in gene expression regulation. Cell 169, 1187–1200 (2017). A review of RNA modifications on coding and noncoding RNAs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cheng, W. et al. CRISPR-Cas9 screens identify the RNA helicase DDX3X as a repressor of C9ORF72 (GGGGCC)n repeat-associated non-AUG translation. Neuron 104, 885–898.e8 (2019). This paper reports CRISPR–Cas9 screens to identify modifiers of DPR protein production from C9orf72 (GGGGCC)n repeat expansion.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Li, Y. et al. Globally reduced N6-methyladenosine (m6A) in C9ORF72-ALS/FTD dysregulates RNA metabolism and contributes to neurodegeneration. Nat. Neurosci. https://doi.org/10.1038/s41593-023-01374-9 (2023)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dysregulation of RNA methylation contributes to neurodegeneration. Nat Neurosci 26, 1322–1323 (2023). https://doi.org/10.1038/s41593-023-01389-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-023-01389-2

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