An RNA-based feed-forward mechanism ensures motor switching in oskar mRNA transport

Regulated recruitment and activity of motor proteins is essential for intracellular transport of cargoes, including messenger ribonucleoprotein complexes (RNPs). Here we show that orchestration ofoskarRNP transport in theDrosophilagermline relies on the interplay of two double-stranded RNA binding proteins, Staufen and the dynein adaptor Egalitarian (Egl). We find that Staufen antagonizes Egl-mediated transport ofoskarmRNA by dynein bothin vitroandin vivo. Following delivery of nurse cell-synthesizedoskarmRNA into the oocyte by dynein, recruitment of Staufen to the RNPs results in dissociation of Egl and a switch to kinesin-1-mediated translocation of the mRNA to its final destination at the posterior pole of the oocyte. We additionally show that Egl associates withstaufen(stau)mRNA in the nurse cells, mediating its enrichment and translation in the ooplasm. Our observations identify a novel feed-forward mechanism, whereby dynein-dependent accumulation ofstaumRNA, and thus protein, in the oocyte enables motor switching onoskarRNPs by downregulating dynein activity.