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M6A/m-Seq of mouse adult cortex after acute stress

ABSTRACT: m6A/m-Seq of mouse adult cortex after acute stress

PROVIDER: PRJNA453975 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7074300_1.fastq.gz	Fastqsanger.gz
	SRR7074300_2.fastq.gz	Fastqsanger.gz
	SRR7074310_1.fastq.gz	Fastqsanger.gz
	SRR7074310_2.fastq.gz	Fastqsanger.gz
	SRR7074320_1.fastq.gz	Fastqsanger.gz

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m6A/m-Seq of mouse adult cortex after acute stress

Project description: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 are currently unknown. Here, we provide a detailed analysis of the stress-epitranscriptome using m6A/m-Seq of 10-12 w male C57BL/6 mouse cortex of unstressed or acutely stressed mice (4 h after 15 min restraint stress) of 6-7 samples per condition (pooled from 3 mice each). PolyA-RNA-fragments of each sample was processed both as m6A/m-sample (RNA immunoprecipiation RIP with an m6A and m6Am antibody) and RNA-input sample.

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Project description: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 are currently unknown. Here, we investigated the effect of gene deletion of Mettl3, a m6A methyltransferase, and Fto, a m6A and m6Am demethlyase, induced in adulthood in excitatory neurons of the neocortex and hippocampus (Camk2a-Cre Mettl3 or Fto cKO) on the cortical epitranscriptome. PolyA-RNA-fragments from 3-5 replicates per group were processed both as m6A/m-sample (RNA immunoprecipiation RIP with an m6A and m6Am antibody) and RNA-input sample.

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Project description: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 are 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 alter the m6A/m epitranscriptome, increase fear memory, alter the transcriptome response to fear and synaptic plasticity. Moreover, we report that regulation of m6A/m is impaired in major depressive disorder (MDD) 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.

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