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oai:repisalud.isciii.es:20.500.12105/78772024-11-29T21:29:36Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Pérez-Guijarro, Eva author Karras, Panagiotis author Cifdaloz, Metehan author Martínez-Herranz, Raúl author Cañón, Estela author Graña Castro, Osvaldo author Horcajada-Reales, Celia author Alonso-Curbelo, Direna author Calvo, Tonantzin G author Gómez-López, Gonzalo author Bellora, Nicolas author Riveiro-Falkenbach, Erica author Ortiz-Romero, Pablo L author Rodríguez-Peralto, José L author Maestre L, Lorena author Roncador, Giovanna author de Agustín Asensio, Juan C author Goding, Colin R author Eyras, Eduardo author Megias Vazquez, Diego author Méndez, Raúl author Soengas, MS author 2016 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. Nat Commun. 2016 ;7:13418 2041-1723 http://hdl.handle.net/20.500.12105/7877 27857118 10.1038/ncomms13418 2041-1723 Nature communications Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers