m6A controls neurogenesis and sex determination in Drosophila via its nuclear reader protein YT521-B [RNA-Seq, whole flies]

N6-methyladenosine RNA (m6A) is the most abundant internal mRNA modification in mammals. While its role in the regulation of posttranscriptional gene expression is beginning to be unveiled, its function during development of complex organisms is poorly understood. Here, we identify Spenito as a novel member of the methyltransferase complex and show that m6A in Drosophila is necessary for proper synaptic growth, and in regulation of early steps of pre-mRNA splicing. Splicing of Sex-lethal and of its downstream targets are defective in animals lacking m6A, revealing also important roles in sex determination and dosage compensation. Finally, we implicate the nuclear m6A reader protein, YT521-B, as a crucial effector of m6A modifications in vivo. Altogether, our work provides important novel insights into m6A biology through identification and characterization of both m6A-writing and -reading proteins in Drosophila and their effects on splicing, neurogenesis and sex-determination within the context of the whole animal. Overall design: RNA seq in Drosophila melanogaster (flies) (3 Conditions, triplicates)

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Lence T, Akhtar J, Bayer M, Schmid K, Spindler L, Ho CH, Kreim N, Andrade-Navarro MA, Poeck B, Helm M, Roignant JY