Structure of Drosophila Oskar reveals a novel RNA binding protein

Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11541-6. doi: 10.1073/pnas.1515568112. Epub 2015 Aug 31.

Abstract

Oskar (Osk) protein plays critical roles during Drosophila germ cell development, yet its functions in germ-line formation and body patterning remain poorly understood. This situation contrasts sharply with the vast knowledge about the function and mechanism of osk mRNA localization. Osk is predicted to have an N-terminal LOTUS domain (Osk-N), which has been suggested to bind RNA, and a C-terminal hydrolase-like domain (Osk-C) of unknown function. Here, we report the crystal structures of Osk-N and Osk-C. Osk-N shows a homodimer of winged-helix-fold modules, but without detectable RNA-binding activity. Osk-C has a lipase-fold structure but lacks critical catalytic residues at the putative active site. Surprisingly, we found that Osk-C binds the 3'UTRs of osk and nanos mRNA in vitro. Mutational studies identified a region of Osk-C important for mRNA binding. These results suggest possible functions of Osk in the regulation of stability, regulation of translation, and localization of relevant mRNAs through direct interaction with their 3'UTRs, and provide structural insights into a novel protein-RNA interaction motif involving a hydrolase-related domain.

Keywords: 3′UTR; Oskar; RNA-binding; germ cell; structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Alleles
  • Animals
  • Body Patterning / genetics
  • Catalytic Domain
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Germ Cells / cytology
  • Models, Molecular
  • Mutation
  • Oocytes / metabolism
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism*
  • Static Electricity
  • X-Ray Diffraction

Substances

  • 3' Untranslated Regions
  • Drosophila Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • osk protein, Drosophila

Associated data

  • PDB/5CD7
  • PDB/5CD8
  • PDB/5CD9