Structure of Drosophila Oskar reveals a novel RNA binding protein

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 predicte...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-09, Vol.112 (37), p.11541-11546
Main Authors: Yang, Na, Yu, Zhenyu, Hu, Menglong, Wang, Mingzhu, Lehmann, Ruth, Xu, Rui-Ming
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Alleles
Animals
Biological Sciences
Body Patterning - genetics
Catalytic Domain
Crystal structure
Drosophila
Drosophila melanogaster - genetics
Drosophila melanogaster - metabolism
Drosophila Proteins - metabolism
Germ Cells - cytology
Insects
Lotus
Models, Molecular
Mutation
Oocytes - metabolism
Protein Binding
Protein Multimerization
Protein Structure, Secondary
Ribonucleic acid
RNA
RNA, Messenger - metabolism
RNA-Binding Proteins - metabolism
RNA-protein interactions
Static Electricity
X-Ray Diffraction
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1515568112