In this study, Knuckles et al. identified Flacc/Zc3h13 as a novel interactor of m 6A methyltransferase complex components in Drosophila and mice. They show that Flacc promotes the recruitment of the methyltransferase to mRNA by bridging Fl(2)d to the mRNA-binding factor Nito, providing novel insights into the conservation and regulation of the m 6A machinery.
N 6-methyladenosine (m 6A) is the most abundant mRNA modification in eukaryotes, playing crucial roles in multiple biological processes. m 6A is catalyzed by the activity of methyltransferase-like 3 (Mettl3), which depends on additional proteins whose precise functions remain poorly understood. Here we identified Zc3h13 (zinc finger CCCH domain-containing protein 13)/Flacc [Fl(2)d-associated complex component] as a novel interactor of m 6A methyltransferase complex components in Drosophila and mice. Like other components of this complex, Flacc controls m 6A levels and is involved in sex determination in Drosophila. We demonstrate that Flacc promotes m 6A deposition by bridging Fl(2)d to the mRNA-binding factor Nito. Altogether, our work advances the molecular understanding of conservation and regulation of the m 6A machinery.