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Epitranscriptomic Dysregulation in Stress-induced Psychopathologies

Dan Ohtan Wang, Kandarp Joshi, Anand Gururajan
doi: https://doi.org/10.1101/2021.02.17.431575
Dan Ohtan Wang
1Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan
2Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China
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Kandarp Joshi
1Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Kyoto, Japan
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Anand Gururajan
3Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, New South Wales, Australia
4Brain & Mind Centre, The University of Sydney, New South Wales, Australia
5School of Psychology, Faculty of Science, The University of Sydney, New South Wales, Australia
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  • For correspondence: anand.gururajan@sydney.edu.au
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Abstract

To date, over 100 different chemical modifications to RNA have been identified. Collectively known as the epitranscriptome, these modifications function to regulate RNA stability and as such, represent another mechanistic layer of post-transcriptional gene regulation. N6-methyladenosine (m6A) is the most common RNA modification in the mammalian brain and has been implicated in a number of processes relevant to neurodevelopment, brain function and behaviour. Here, following brief descriptions on epitranscriptomic mechanisms, we will review the literature on the potential functions of the m6A-methylome in fine-tuning gene expression which include prescribing localisation of transcripts in distal compartments as well as interactions with microRNAs and long non-coding RNAs. We will then discuss findings from rodent and human studies for stress-induced disorders - major depression and post-traumatic stress disorder – which support a hypothesis for a dysregulation of the m6A-methylome and the m6A-machinery in the pathophysiology. To support this, we have included a bioinformatic analysis of publicly available single-cell RNA-sequencing and bulk transcriptomics datasets which suggests an altered m6A-methylome as a consequence of dysregulated cell- and regionally-specific expression of key enzymes involved in the ‘writing, reading and erasing’ of m6A. We hope this review will generate further interest in the field of epitranscriptomics, opening up new lines of research into its involvement in psychiatric disorders.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://github.com/kandarpRJ/epi_psych_metaanalysis

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 17, 2021.
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Epitranscriptomic Dysregulation in Stress-induced Psychopathologies
Dan Ohtan Wang, Kandarp Joshi, Anand Gururajan
bioRxiv 2021.02.17.431575; doi: https://doi.org/10.1101/2021.02.17.431575
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Epitranscriptomic Dysregulation in Stress-induced Psychopathologies
Dan Ohtan Wang, Kandarp Joshi, Anand Gururajan
bioRxiv 2021.02.17.431575; doi: https://doi.org/10.1101/2021.02.17.431575

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