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

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Basquin,  Claire
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Lazzaretti, D., Veith, K., Kramer, K., Basquin, C., Urlaub, H., Iron, U., et al. (2016). The bicoid mRNA localization factor Exuperantia is an RNA-binding pseudonuclease. Nature Structural and Molecular Biology, 23, 705-713. doi:10.1038/nsmb.3254.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-9EF3-4
Abstract
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.