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 Canõn; Osvaldo Granã; 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 Megiás; Raúl Méndez; Maria S. Soengas

doi:10.1038/ncomms13418

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 Canõn, Osvaldo Granã, 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 MegiásRaúl Méndez, Maria S. Soengas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

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.

Original language	English
Article number	13418
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13418
Publication status	Published - 18 Nov 2016
Externally published	Yes

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Pérez-Guijarro, E., Karras, P., Cifdaloz, M., Martínez-Herranz, R., Canõn, E., Granã, O., Horcajada-Reales, C., Alonso-Curbelo, D., Calvo, T. G., Gómez-López, G., Bellora, N., Riveiro-Falkenbach, E., Ortiz-Romero, P. L., Rodríguez-Peralto, J. L., Maestre, L., Roncador, G., De Agustín Asensio, J. C., Goding, C. R., Eyras, E., ... Soengas, M. S. (2016). Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers. Nature Communications, 7, Article 13418. https://doi.org/10.1038/ncomms13418

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title = "Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers",

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.",

author = "Eva P{\'e}rez-Guijarro and Panagiotis Karras and Metehan Cifdaloz and Ra{\'u}l Mart{\'i}nez-Herranz and Estela Can{\~o}n and Osvaldo Gran{\~a} and Celia Horcajada-Reales and Direna Alonso-Curbelo and Calvo, {Tonantzin G.} and Gonzalo G{\'o}mez-L{\'o}pez and Nicolas Bellora and Erica Riveiro-Falkenbach and Ortiz-Romero, {Pablo L.} and Rodr{\'i}guez-Peralto, {Jos{\'e} L.} and Lorena Maestre and Giovanna Roncador and {De Agust{\'i}n Asensio}, {Juan C.} and Goding, {Colin R.} and Eduardo Eyras and Diego Megi{\'a}s and Ra{\'u}l M{\'e}ndez and Soengas, {Maria S.}",

note = "Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = nov,

day = "18",

doi = "10.1038/ncomms13418",

language = "English",

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journal = "Nature Communications",

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Pérez-Guijarro, E, Karras, P, Cifdaloz, M, Martínez-Herranz, R, Canõn, E, Granã, O, Horcajada-Reales, C, Alonso-Curbelo, D, Calvo, TG, Gómez-López, G, Bellora, N, Riveiro-Falkenbach, E, Ortiz-Romero, PL, Rodríguez-Peralto, JL, Maestre, L, Roncador, G, De Agustín Asensio, JC, Goding, CR, Eyras, E, Megiás, D, Méndez, R & Soengas, MS 2016, 'Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers', Nature Communications, vol. 7, 13418. https://doi.org/10.1038/ncomms13418

TY - JOUR

T1 - Lineage-specific roles of the cytoplasmic polyadenylation factor CPEB4 in the regulation of melanoma drivers

AU - Pérez-Guijarro, Eva

AU - Karras, Panagiotis

AU - Cifdaloz, Metehan

AU - Martínez-Herranz, Raúl

AU - Canõn, Estela

AU - Granã, Osvaldo

AU - Horcajada-Reales, Celia

AU - Alonso-Curbelo, Direna

AU - Calvo, Tonantzin G.

AU - Gómez-López, Gonzalo

AU - Bellora, Nicolas

AU - Riveiro-Falkenbach, Erica

AU - Ortiz-Romero, Pablo L.

AU - Rodríguez-Peralto, José L.

AU - Maestre, Lorena

AU - Roncador, Giovanna

AU - De Agustín Asensio, Juan C.

AU - Goding, Colin R.

AU - Eyras, Eduardo

AU - Megiás, Diego

AU - Méndez, Raúl

AU - Soengas, Maria S.

PY - 2016/11/18

Y1 - 2016/11/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84996587351&partnerID=8YFLogxK

U2 - 10.1038/ncomms13418

DO - 10.1038/ncomms13418

M3 - Article

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13418

ER -

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

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