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The Role of m6A/m-RNA Methylation in Stress Response Regulation.


ABSTRACT: N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed m6A/m, in the stress response in the adult brain in vivo is currently unknown. Here, we provide a detailed analysis of the stress epitranscriptome using m6A/m-seq, global and gene-specific m6A/m measurements. We show that stress exposure and glucocorticoids region and time specifically alter m6A/m and its regulatory network. We demonstrate that deletion of the methyltransferase Mettl3 or the demethylase Fto in adult neurons alters the m6A/m epitranscriptome, increases fear memory, and changes the transcriptome response to fear and synaptic plasticity. Moreover, we report that regulation of m6A/m is impaired in major depressive disorder patients following glucocorticoid stimulation. Our findings indicate that brain m6A/m represents a novel layer of complexity in gene expression regulation after stress and that dysregulation of the m6A/m response may contribute to the pathophysiology of stress-related psychiatric disorders.

SUBMITTER: Engel M 

PROVIDER: S-EPMC6069762 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) and N<sup>6</sup>,2'-O-dimethyladenosine (m<sup>6</sup>Am) are abundant mRNA modifications that regulate transcript processing and translation. The role of both, here termed m<sup>6</sup>A/m, in the stress response in the adult brain in vivo is currently unknown. Here, we provide a detailed analysis of the stress epitranscriptome using m<sup>6</sup>A/m-seq, global and gene-specific m<sup>6</sup>A/m measurements. We show that stress exposure and gluc  ...[more]

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