The tRNA methyltransferase dTrmt10A impacts m6A levels and the stress response in the Drosophila brain

The tRNA methyltransferase TRMT10A was previously shown modulating the level of N6-methyladenosine (m6A) in polyadenylated RNA (polyA+ RNA). Here, we focus on the function of the Drosophila homolog of human TRMT10A, CG14618/dTrmt10A, and its impact on m6A regulation in the Drosophila brain and acute stress response. Using m6A-IP RNA sequencing from head tissue, we find that altering the levels of dTrmt10A modulates the levels of m6A on polyA+ RNA in the brain. Specifically, dTrmt10A affects m6A levels on transcripts enriched for signaling pathways, with a particular impact on 3' UTR m6A in response to heat shock. Furthermore, our findings indicate that upregulation of dTrmt10A results in a global decrease in m6A levels and decreases resilience to acute heat stress. Collectively, our data affirm the crucial role of m6A in the biological response of the brain to stress, and reveal that dTrmt10A acts as an additional regulator of m6A in the Drosophila brain and stress response. Overall design: head m6A-IP used to investigate the role of the m6A RNA modification in heat shock stress and dTrmt10A knockdown and upregulation.