N-methyladenosine (mA), the most prevalent internal modification on eukaryotic mRNA, plays an essential role in various stress responses. The brain is uniquely vulnerable to cellular stress, thus defining how mA sculpts the brain's susceptibility may provide insight to brain aging and disease-related stress. Here we investigate the impact of mA mRNA methylation in the adult Drosophila brain with stress. We show that mA is enriched in the adult brain and increases with heat stress. Through mA-immunoprecipitation sequencing, we show 5'UTR Mettl3-dependent mA is enriched in transcripts of neuronal processes and signaling pathways that increase upon stress. Mettl3 knockdown results in increased levels of mA targets and confers resilience to stress. We find loss of Mettl3 results in decreased levels of nuclear mA reader Ythdc1, and knockdown of Ythdc1 also leads to stress resilience. Overall, our data suggest that mA modification in Drosophila dampens the brain's biological response to stress.
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| http://dx.doi.org/10.1038/s41467-022-33085-3 | DOI Listing |
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