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