The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division

Nat Commun. 2015 Oct 1;6:8381. doi: 10.1038/ncomms9381.

Abstract

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 fifth double-stranded RNA (dsRNA)-binding domain (dsRBD5) of Stau is necessary and sufficient for binding to a coiled-coil region of Mira cargo-binding domain (CBD). The crystal structure of Mira514-595/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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Gene Expression Regulation / physiology*
  • Models, Molecular
  • Neurons / cytology
  • Neurons / physiology*
  • Protein Conformation
  • Protein Transport / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Mira protein, Drosophila
  • RNA-Binding Proteins
  • stau protein, Drosophila

Associated data

  • PDB/5CFF