Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers

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  • dc.contributor.author Pérez-Guijarro, Evaca
  • dc.contributor.author Bellora Pereyra, Nicolásca
  • dc.contributor.author Eyras Jiménez, Eduardoca
  • dc.contributor.author Soengas, María S.ca
  • dc.date.accessioned 2017-03-10T11:14:01Z
  • dc.date.available 2017-03-10T11:14:01Z
  • dc.date.issued 2016
  • dc.description.abstract Nuclear 3’-end-polyadenylation is essential for the transport, stability and translation of virtually all eukaryotic mRNAs. Poly(A) tail extension can also occur in the cytoplasm, but the transcripts involved are incompletely understood, particularly in cancer. Here we identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma. CPEB4 is upregulated early in melanoma progression, as defined by computational and histological analyses. Melanoma cells are distinct from other tumour cell types in their dependency on CPEB4, not only to prevent mitotic aberrations, but to progress through G1/S cell cycle checkpoints. RNA immunoprecipitation, sequencing of bound transcripts and poly(A) length tests link the melanoma-specific functions of CPEB4 to signalling hubs specifically enriched in this disease. Essential in these CPEB4-controlled networks are the melanoma drivers MITF and RAB7A, a feature validated in clinical biopsies. These results provide new mechanistic links between cytoplasmic polyadenylation and lineage specification in melanoma.
  • dc.description.sponsorship M.S.S. was funded by Marató TVE and Consolider RNAREG (CSD2009-00080), and SAF2014-56868-R (Spanish Ministry of Economy and Innovation). R.M. was supported by Fundación Botín, by the Banco Santander through its Santander Universities Global Division, and by grants from the Spanish Ministry of Economy and Innovation (BFU2011–30121 and Consolider RNAREG (CSD2009-00080). J.L.R.-P. was funded by grant FIS 2014/1737 from the Spanish Ministry of Health, P.L.O.-R. by FIS 14/1784; and N.B. and E.E. by MINECO and FEDER (BIO2014-52566-R), as well as by Consolider RNAREG (CSD2009-00080), by AGAUR (2014-SGR1121) and by the Sandra Ibarra Foundation for Cancer (FSI2013). C.R.G was funded by Ludwig Institute for Cancer Research. E.P.-G., D.A.-C. and R.M.-H. are recipients of Scientists in Training predoctoral fellowships from the Spanish Ministry of Science and Innovation. P.K and M.C. are funded by a predoctoral fellowship from Fundación La Caixa. E.R.-F. is the recipient of a postdoctoral fellowship from ‘Fundación Científica de la Asociación Española Contra el Cáncer’ and supported by FMM-2013/0075 of Fundacion Mutua Madrileña.
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Pérez-Guijarro E, Karras P, Cifdaloz M, Martínez-Herranz R, Cañón E, Graña O. Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers. Nature Communications. 2016;7:13418. DOI: 10.1038/ncomms13418
  • dc.identifier.doi http://dx.doi.org/10.1038/ncomms13418
  • dc.identifier.issn 2041-1723
  • dc.identifier.uri http://hdl.handle.net/10230/28204
  • dc.language.iso eng
  • dc.publisher Nature Publishing Groupca
  • dc.relation.ispartof Nature Communications. 2016;7:13418
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2014-52566-R
  • dc.rights © Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Melanoma
  • dc.subject.keyword Oncology
  • dc.title Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma driversca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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