The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Dynamic m6A modification regulates local translation of mRNA in axons
Open accessAbstract
N6-methyladenosine (m6A) is a reversible modification in mRNA and has been shown to regulate processing, translation and decay of mRNA. However, the roles of m6A modification in neuronal development are still not known. Here, we found that the m6A eraser FTO is enriched in axons and can be locally translated. Axon-specific inhibition of FTO by rhein, or compartmentalized siRNA knockdown of Fto in axons led to increases of m6A levels. GAP-43 mRNA is modified by m6A and is a substrate of FTO in axons. Loss-of-function of this non-nuclear pool of FTO resulted in increased m6A modification and decreased local translation of axonal GAP-43 mRNA, which eventually repressed axon elongation. Mutation of a predicted m6A site in GAP-43 mRNA eliminated its m6A modification and exempted regulation of its local translation by axonal FTO. This work showed an example of dynamic internal m6A demethylation of non-nuclear localized mRNA by the demethylase FTO. Regulation of m6A modification of axonal mRNA by axonal FTO might be a general mechanism to control their local translation in neuronal development.
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Cites
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Cited by
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The m6A epitranscriptome: transcriptome plasticity in brain development and function
Livneh, I., Moshitch-Moshkovitz, S., Amariglio, N., Rechavi, G., & Dominissini, D. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0244-z · Cited by 330
METTL3-mediated m6A modification is required for cerebellar development
Wang, C.-X., Cui, G.-S., Liu, X., Xu, K., Wang, M., Zhang, X.-X., Jiang, L.-Y., Li, A., Yang, Y., Lai, W.-Y., et al. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2004880 · Cited by 291
The proteins of mRNA modification: writers, readers, and erasers
Flamand, M. N., Tegowski, M., & Meyer, K. D. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-052521-035330 · Cited by 164
Nguyen, T. B., Miramontes, R., Chillon-Marinas, C., Maimon, R., Vazquez-Sanchez, S., Lau, A. L., McClure, N. R., England, W. E., Singha, M., Stocksdale, J. T., et al. (2023) · doi:10.1101/2023.10.31.565004 · Cited by 15
Metadata
- Authors
- Yu, J., Chen, M., Huang, H., Zhu, J., Song, H., Zhu, J., Park, J., & Ji, S.-J.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-11-23
- Volume
- 46
- Issue
- 3
- Pages
- 1412-1423
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- OpenAlex
- W2769856951
- Cited by
- 325
- References
- 71
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- gold
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