PT  - JOURNAL ARTICLE
AU  - Mareen Engel
AU  - Simone Röh
AU  - Carola Eggert
AU  - Paul M. Kaplick
AU  - Lisa Tietze
AU  - Janine Arloth
AU  - Peter Weber
AU  - Monika Rex-Haffner
AU  - Mira Jakovcevski
AU  - Manfred Uhr
AU  - Matthias Eder
AU  - Carsten T. Wotjak
AU  - Mathias V. Schmidt
AU  - Jan M. Deussing
AU  - Elisabeth B. Binder
AU  - Alon Chen
TI  - The role of m<sup>6</sup>A-RNA methylation in stress response regulation
AID  - 10.1101/200402
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 200402
4099  - http://biorxiv.org/content/early/2017/10/09/200402.short
4100  - http://biorxiv.org/content/early/2017/10/09/200402.full
AB  - N6-Methyladenosine (m6A) is an abundant internal RNA modification that regulates transcript processing and translation. The regulation of brain m6A by stressful stimuli in vivo and its role in the stress response are currently unknown.Here, we provide a detailed analysis of the stress-epitranscriptome using m6A-Seq, global and gene-specific m6A measurements. We show that stress exposure and glucocorticoids alter m6A and its regulatory network in a region- and time-specific manner. We demonstrate that depletion of the methyltransferase Mettl3 and the demethylase Fto in adult neurons increases fear memory, and alters the transcriptome response to fear as well as synaptic plasticity. Finally, we report that regulation of m6A is impaired in major depressive disorder patients following glucocorticoid receptor activation.Our findings indicate that brain m6A represents a novel layer of complexity in gene expression regulation after stress and that dysregulation of the m6A-response may contribute to the pathophysiology of stress-related psychiatric disorders.Highlightsm6A and m6Am RNA methylation in the adult mouse brain is largely stress-regulatedm6A regulation is gene- and brain-area-specific and time-dependentMettl3 and Fto-KO alter fear memory, transcriptome response and synaptic plasticityThe m6A-glucocorticoid-response is impaired in major depressive disorder patientseTOCblurb Engel et al. demonstrate that an abundant mRNA modification, m6A, is widely regulated after stress in the mouse brain. Manipulating m6A-enzymes enhances their memory to stressful events. They further show that m6A is dysregulated in blood of psychiatric patients.