Structure of Drosophila Oskar reveals a novel RNA binding protein

Proceedings of the National Academy of Sciences of the United States of America
Na YangRui-Ming Xu

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.

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Citations

Apr 19, 2016·Current Opinion in Insect Science·Honghu Quan, Jeremy A Lynch
Jun 18, 2016·Current Opinion in Structural Biology·Stephanie HelderJoel P Mackay
Apr 21, 2016·Development·Karuna Sampath, Anne Ephrussi
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Nov 7, 2018·PLoS Genetics·Pritesh KrishnakumarRoland Dosch
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Jun 21, 2019·Traffic·Tatjana Trcek, Ruth Lehmann
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Aug 9, 2020·Nucleic Acids Research·Deqiang DingChen Chen
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Feb 9, 2021·Wiley Interdisciplinary Reviews. RNA·Nivedita Mukherjee, Chandrama Mukherjee
Feb 6, 2021·Biological Chemistry·Jana KubíkováMandy Jeske
May 29, 2020·Molecular Cell·Tatjana TrcekRuth Lehmann

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