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Title:	Hrp48 and eIF3d contribute to msl-2 mRNA translational repression
Author:	Szóstak, Emilia, 1984-; García Beyaert, Marina, 1983-; Guitart, Tanit; Graindorge, Antoine; Coll, Olga; Gebauer, Fátima
Abstract:	Translational repression of msl-2 mRNA in females of Drosophila melanogaster is an essential step in the regulation of X-chromosome dosage compensation. Repression is orchestrated by Sex-lethal (SXL), which binds to both untranslated regions (UTRs) of msl-2 and inhibits translation initiation by poorly understood mechanisms. Here we identify Hrp48 as a SXL co-factor. Hrp48 binds to the 3' UTR of msl-2 and is required for optimal repression by SXL. Hrp48 interacts with eIF3d, a subunit of the eIF3 translation initiation complex. Reporter and RNA chromatography assays showed that eIF3d binds to msl-2 5' UTR, and is required for efficient translation and translational repression of msl-2 mRNA. In line with these results, eIF3d depletion -but not depletion of other eIF3 subunits- de-represses msl-2 expression in female flies. These data are consistent with a model where Hrp48 inhibits msl-2 translation by targeting eIF3d. Our results uncover an important step in the mechanism of msl-2 translation regulation, and illustrate how general translation initiation factors can be co-opted by RNA binding proteins to achieve mRNA-specific control.
Abstract:	Spanish Ministry of Economy and Competitiveness MINECO and the European Regional Development Fund (ERDF) [BFU2012-37135, BFU2015-68741, Consolider CSD2009-00080]; Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’ [SEV-2012-0208]; La Caixa Foundation (to M.G.-B.); Fondation pour la Recherche Médicale (FRM) (to A.G.). Funding for open access charge: Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2015-68741].
Rights:	© The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com http://creativecommons.org/licenses/by-nc/4.0/
Document type:	Article Article - Published version
Published by:	Oxford University Press
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