A neural m⁶A/Ythdf pathway is required for learning and memory in Drosophila.

ABSTRACT: Epitranscriptomic modifications can impact behavior. Here, we used Drosophila melanogaster to study N⁶-methyladenosine (m⁶A), the most abundant modification of mRNA. Proteomic and functional analyses confirm its nuclear (Ythdc1) and cytoplasmic (Ythdf) YTH domain proteins as major m⁶A binders. Assays of short term memory in m⁶A mutants reveal neural-autonomous requirements of m⁶A writers working via Ythdf, but not Ythdc1. Furthermore, m⁶A/Ythdf operate specifically via the mushroom body, the center for associative learning. We map m⁶A from wild-type and Mettl3 mutant heads, allowing robust discrimination of Mettl3-dependent m⁶A sites that are highly enriched in 5' UTRs. Genomic analyses indicate that Dr

SUBMITTER: Kan L 

PROVIDER: S-EPMC7935873 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature