Hrp48 and eIF3d contribute to msl-2 mRNA translational repression

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  • dc.contributor.author Szóstak, Emilia, 1984-
  • dc.contributor.author García Beyaert, Marina, 1983-
  • dc.contributor.author Guitart, Tanit
  • dc.contributor.author Graindorge, Antoine
  • dc.contributor.author Coll, Olga
  • dc.contributor.author Gebauer, Fátima
  • dc.date.accessioned 2019-11-26T07:54:05Z
  • dc.date.available 2019-11-26T07:54:05Z
  • dc.date.issued 2018
  • dc.description.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.
  • dc.description.sponsorship 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].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Szostak E, García-Beyaert M, Guitart T, Graindorge A, Coll O, Gebauer F. Hrp48 and eIF3d contribute to msl-2 mRNA translational repression. Nucleic Acids Res. 2018;46(8):4099-113. DOI: 10.1093/nar/gky246
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gky246
  • dc.identifier.issn 0305-1048
  • dc.identifier.uri http://hdl.handle.net/10230/42979
  • dc.language.iso eng
  • dc.publisher Oxford University Press
  • dc.relation.ispartof Nucleic Acids Research. 2018;46(8):4099-113
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-37135
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68741
  • dc.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
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.title Hrp48 and eIF3d contribute to msl-2 mRNA translational repression
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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