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

• Published in: Nature communications 2016-11, Vol.7 (1), p.13418-13418, Article 13418
• Main Authors: Pérez-Guijarro, Eva, Karras, Panagiotis, Cifdaloz, Metehan, Martínez-Herranz, Raúl, Cañón, Estela, Graña, Osvaldo, Horcajada-Reales, Celia, Alonso-Curbelo, Direna, Calvo, Tonantzin G., Gómez-López, Gonzalo, Bellora, Nicolas, Riveiro-Falkenbach, Erica, Ortiz-Romero, Pablo L., Rodríguez-Peralto, José L., Maestre, Lorena, Roncador, Giovanna, de Agustín Asensio, Juan C., Goding, Colin R., Eyras, Eduardo, Megías, Diego, Méndez, Raúl, Soengas, María S.
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/105; 13/106; 13/109; 13/2; 13/31; 14/1; 14/19; 631/67/1813/1634; 692/4028; Animals; Cancer research; Cell Cycle; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Gene Silencing; Hospitals; Humanities and Social Sciences; Humans; Medical research; Melanoma; Melanoma - genetics; Melanoma - metabolism; Metastasis; Mice; multidisciplinary; Neoplasms, Experimental; Oncology; Proteins; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Science; Science (multidisciplinary); Skin cancer; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13418

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. Cytoplasmic polyadenylated transcripts have been poorly characterized, particularly in cancer. Here the authors identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma and show that it controls melanoma drivers MITF and RAB27A.