bioRxiv preprint doi: https://doi.org/10.1101/572156; this version posted March 9, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The solution structure of Dead End bound to AU-rich RNA reveals an unprecedented mode of tandem RRM-RNA recognition required for mRNA repression Authors Malgorzata M. Duszczyk1*, Harry Wischnewski2, Tamara Kazeeva1, Fionna E. Loughlin1,4, Christine von Schroetter1, Ugo Pradère3, Jonathan Hall3, Constance Ciaudo2*, Frédéric H.-T. Allain1,5* Affiliations 1Institute of Molecular Biology and Biophysics and 2Institute of Molecular Health Sciences, Department of Biology, 3Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093, Zürich, Switzerland 4Present Address: Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800 VIC, Australia 5Lead Contact Contact Information *To whom correspondence should be addressed. E-mail:
[email protected] (M.M.D.),
[email protected] (C.C.),
[email protected] (F.H.- T.A.) Abstract Dead End (DND1) is an RNA-binding protein essential for germline development through its role in the clearance of AU-rich mRNAs. Here, we present the solution structure of its tandem RNA Recognition Motifs (RRMs) bound to AU-rich RNA. The structure reveals how an NYAYUNN element is recognized in agreement with recent genome-wide studies. RRM1 acts as a main binding platform, including unusual helical and -hairpin extensions to the canonical RRM fold.