Nucleic Acids Research Advance Access originally published online on March 18, 2009
Nucleic Acids Research 2009 37(9):2974-2983; doi:10.1093/nar/gkp173
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Nucleic Acids Research, 2009, Vol. 37, No. 9 2974-2983
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
The RRM domain in GW182 proteins contributes to miRNA-mediated gene silencing
Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany
*To whom correspondence should be addressed. Tel: +49 7071 601 1350; Fax: +49 7071 601 1353; Email: elisa.izaurralde{at}tuebingen.mpg.de
Received February 8, 2009. Revised March 2, 2009. Accepted March 3, 2009.
Proteins of the GW182 family interact with Argonaute proteins and are required for miRNA-mediated gene silencing. These proteins contain two structural domains, an ubiquitin-associated (UBA) domain and an RNA recognition motif (RRM), embedded in regions predicted to be unstructured. The structure of the RRM of Drosophila melanogaster GW182 reveals that this domain adopts an RRM fold, with an additional C-terminal 
-helix. The helix lies on the β-sheet surface, generally used by these domains to bind RNA. This, together with the absence of aromatic residues in the conserved RNP1 and RNP2 motifs, and the lack of general affinity for RNA, suggests that the GW182 RRM does not bind RNA. The domain may rather engage in protein interactions through an unusual hydrophobic cleft exposed on the opposite face of the β-sheet. We further show that the GW182 RRM is dispensable for P-body localization and for interaction of GW182 with Argonaute-1 and miRNAs. Nevertheless, its deletion impairs the silencing activity of GW182 in a miRNA target-specific manner, indicating that this domain contributes to silencing. The conservation of structural and surface residues suggests that the RRM domain adopts a similar fold with a related function in insect and vertebrate GW182 family members.
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