Xio is a component of the Drosophila sex determination pathway and RNA N⁶-methyladenosine methyltransferase complex.

N⁶-methyladenosine (m⁶A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in Drosophila sex determination by modifying Sex-lethal (Sxl) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, CG7358, and rename it xio according to its loss-of-function female-to-male transformation phenotype. xio encodes a conserved ubiquitous nuclear protein of unknown function. We show that Xio colocalizes and interacts with all previously known m⁶A writer complex subunits (METTL3, METTL14, Fl(2)d/WTAP, Vir/KIAA1429, and Nito/Rbm15) and that loss of xio is associated with phenotypes that resemble other m⁶A factors, such as sexual transformations, Sxl splicing defect, held-out wings, flightless flies, and reduction of m⁶A levels. Thus, Xio encodes a member of the m⁶A methyltransferase complex involved in mRNA modification. Since its ortholog ZC3H13 (or KIAA0853) also associates with several m⁶A writer factors, the function of Xio in the m⁶A pathway is likely evolutionarily conserved.

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