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

EVA PÉREZ-GUIJARRO; PANAGIOTIS KARRAS; METEHAN CIFDALOZ; RAÚL MARTÍNEZ-HERRANZ; ESTELA CAÑÓN; OSVALDO GRAÑA; CELIA HORCAJADA-REALES; DIRENA ALONSO-CURBELO; TONANTZIN G. CALVO; GONZALO GÓMEZ-LÓPEZ; NICOLAS BELLORA; ERICA RIVEIRO-FALKENBACH; PABLO L. ORTIZ-ROMERO; JOSÉ L. RODRÍGUEZ-PERALTO; LORENA MAESTRE; GIOVANNA RONCADOR; JUAN C. DE AGUSTÍN ASENSIO; COLIN R. GODING; EDUARDO EYRAS; DIEGO MEGÍAS; RAUL MENDEZ; MARÍA S. SOENGAS

NATURE COMMUNICATIONS

Springer Nature

Lugar: Londres; Año: 2016

2041-1723

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) inmalignant 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.