Xio is a component of the <i>Drosophila</i> sex determination pathway and RNA <i>N</i>⁶-methyladenosine methyltransferase complex.

Abstract

<i>N</i>⁶-methyladenosine (m⁶A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in <i>Drosophila</i> sex determination by modifying <i>Sex-lethal</i> (<i>Sxl</i>) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, <i>CG7358</i>, and rename it <i>xio</i> according to its loss-of-function female-to-male transformation phenotype. <i>xio</i> 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 <i>xio</i> is associated with phenotypes that resemble other m⁶A factors, such as sexual transformations, <i>Sxl</i> 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.