Staufen2-mediated RNA recognition and localization requires combinatorial action of multiple domains

Nat Commun. 2019 Apr 10;10(1):1659. doi: 10.1038/s41467-019-09655-3.


Throughout metazoans, Staufen (Stau) proteins are core factors of mRNA localization particles. They consist of three to four double-stranded RNA binding domains (dsRBDs) and a C-terminal dsRBD-like domain. Mouse Staufen2 (mStau2)-like Drosophila Stau (dmStau) contains four dsRBDs. Existing data suggest that only dsRBDs 3-4 are necessary and sufficient for mRNA binding. Here, we show that dsRBDs 1 and 2 of mStau2 bind RNA with similar affinities and kinetics as dsRBDs 3 and 4. While RNA binding by these tandem domains is transient, all four dsRBDs recognize their target RNAs with high stability. Rescue experiments in Drosophila oocytes demonstrate that mStau2 partially rescues dmStau-dependent mRNA localization. In contrast, a rescue with mStau2 bearing RNA-binding mutations in dsRBD1-2 fails, confirming the physiological relevance of our findings. In summary, our data show that the dsRBDs 1-2 play essential roles in the mRNA recognition and function of Stau-family proteins of different species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Embryo, Nonmammalian
  • Female
  • Mutagenesis, Site-Directed
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / isolation & purification
  • Nerve Tissue Proteins / metabolism*
  • Oocytes
  • Protein Binding
  • Protein Domains / physiology*
  • RNA, Double-Stranded / metabolism*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / isolation & purification
  • RNA-Binding Proteins / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism


  • Drosophila Proteins
  • Nerve Tissue Proteins
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA-Binding Proteins
  • Recombinant Proteins
  • stau2 protein, mouse
  • stau protein, Drosophila