Asymmetric cell division(ACD)is an evolutionarily conserved division mode used by stem and progenitor cells to create two daughter cells with distinct fates.Typically,one daughter cell retains self-renewal ability,and the other daughter cell enters the path of differentiation.During the asymmetric division of Drosophila neuroblasts(NBs),the scaffold Miranda(Mira)coordinates the subcellular distribution of cell-fate determinants including Staufen(Stau)and segregates them into the ganglion mother cells(GMCs).Here we show the RNA-binding deficient dsRBD5 of Stau is necessary and sufficient for binding to a coiled-coil region of Miranda cargo-binding domain(CBD).The crystal structure of Mira/Stau dsRBD5 complex illustrates that Mira forms an elongated parallel coiled-coil dimer,and two dsRBD5 symmetrically bind to the Mira dimer through their exposed β-sheet faces,revealing a previously unrecognized protein interaction mode for dsRBDs.We further demonstrate that the Mira-Stau dsRBD5 interaction is responsible for the asymmetric localization of Stau during Drosophila NB asymmetric divisions.Finally,we find the CBD-mediated dimer assembly is likely a common requirement for Mira to recognize and translocate other cargos including brain tumour(Brat).