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Nat Struct Mol Biol. 2016 Aug;23(8):705-13. doi: 10.1038/nsmb.3254. Epub 2016 Jul 4.

The bicoid mRNA localization factor Exuperantia is an RNA-binding pseudonuclease.

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Max Planck Institute for Developmental Biology, Tübingen, Germany.
Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Bioanalytics, Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.
Max Planck Institute of Biochemistry, Martinsried, Germany.


Anterior patterning in Drosophila is mediated by the localization of bicoid (bcd) mRNA at the anterior pole of the oocyte. Exuperantia (Exu) is a putative exonuclease (EXO) associated with bcd and required for its localization. We present the crystal structure of Exu, which reveals a dimeric assembly with each monomer consisting of a 3'-5' EXO-like domain and a sterile alpha motif (SAM)-like domain. The catalytic site is degenerate and inactive. Instead, the EXO-like domain mediates dimerization and RNA binding. We show that Exu binds RNA directly in vitro, that the SAM-like domain is required for RNA binding activity and that Exu binds a structured element present in the bcd 3' untranslated region with high affinity. Through structure-guided mutagenesis, we show that Exu dimerization is essential for bcd localization. Our data demonstrate that Exu is a noncanonical RNA-binding protein with EXO-SAM-like domain architecture that interacts with its target RNA as a homodimer.

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