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Epitranscriptomic dynamics in brain development and disease

Molecular Psychiatry volume 27, pages 3633–3646 (2022)Cite this article

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Abstract

Distinct cell types are generated at specific times during brain development and are regulated by epigenetic, transcriptional, and newly emerging epitranscriptomic mechanisms. RNA modifications are known to affect many aspects of RNA metabolism and have been implicated in the regulation of various biological processes and in disease. Recent studies imply that dysregulation of the epitranscriptome may be significantly associated with neuropsychiatric, neurodevelopmental, and neurodegenerative disorders. Here we review the current knowledge surrounding the role of the RNA modifications N6-methyladenosine, 5-methylcytidine, pseudouridine, A-to-I RNA editing, 2′O-methylation, and their associated machinery, in brain development and human diseases. We also highlight the need for the development of new technologies in the pursuit of directly mapping RNA modifications in both genome- and single-molecule-level approach.

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Fig. 1: Perturbation of the epitranscriptome is associated with neuropsychiatric disorders and neurodegenerative diseases.
Fig. 2: Role of m6A in neural development.
Fig. 3: Mechanistic detail describing the association between RNA modifications with FMRP and potentially fragile X syndrome.
Fig. 4: Using Nanopore sequencing to detect RNA modifications.

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Acknowledgements

This work was supported in part by National Institutes of Health (NS111602, HG008935, and MH116441 to P.J.)

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  1. Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, 30322, USA

    Andrew M. Shafik, Emily G. Allen & Peng Jin

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A.M.S. wrote the manuscript. E.G.A. and P.J. edited the manuscript.

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Shafik, A.M., Allen, E.G. & Jin, P. Epitranscriptomic dynamics in brain development and disease. Mol Psychiatry 27, 3633–3646 (2022). https://doi.org/10.1038/s41380-022-01570-2

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