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SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation

Synchronisation of translation rates between the mitochondria and their cellular host is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translation uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, the comp...

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Autores principales: Roberto, Vendramin, Yvessa, Verheyden, Hideaki, Ishikawa, Lucas, Goedert, Emilien, Nicolas, Kritika, Saraf, Alexandros, Armaos, Riccardo, Delli Ponti, Keiichi, Izumikawa, Pieter, Mestdagh, Denis, Lafontaine L.J., Gaetano, Tartaglia Gian, Nobuhiro, Takahashi, Jean-Christophe, Marine, Eleonora, Leucci
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223542/
https://www.ncbi.nlm.nih.gov/pubmed/30374086
http://dx.doi.org/10.1038/s41594-018-0143-4
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author Roberto, Vendramin
Yvessa, Verheyden
Hideaki, Ishikawa
Lucas, Goedert
Emilien, Nicolas
Kritika, Saraf
Alexandros, Armaos
Riccardo, Delli Ponti
Keiichi, Izumikawa
Pieter, Mestdagh
Denis, Lafontaine L.J.
Gaetano, Tartaglia Gian
Nobuhiro, Takahashi
Jean-Christophe, Marine
Eleonora, Leucci
author_facet Roberto, Vendramin
Yvessa, Verheyden
Hideaki, Ishikawa
Lucas, Goedert
Emilien, Nicolas
Kritika, Saraf
Alexandros, Armaos
Riccardo, Delli Ponti
Keiichi, Izumikawa
Pieter, Mestdagh
Denis, Lafontaine L.J.
Gaetano, Tartaglia Gian
Nobuhiro, Takahashi
Jean-Christophe, Marine
Eleonora, Leucci
author_sort Roberto, Vendramin
collection PubMed
description Synchronisation of translation rates between the mitochondria and their cellular host is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translation uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, the compensating mechanisms in place in the mitochondria remain elusive. Here we show that the malignant lncRNA SAMMSON promotes a balanced increase in rRNA maturation and protein synthesis in the cytosol and mitochondria by modulating the localisation of CARF, an RNA-binding protein sequestering XRN2 in the nucleoplasm and limiting nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favouring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. This data highlights how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth.
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spelling pubmed-62235422019-04-29 SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation Roberto, Vendramin Yvessa, Verheyden Hideaki, Ishikawa Lucas, Goedert Emilien, Nicolas Kritika, Saraf Alexandros, Armaos Riccardo, Delli Ponti Keiichi, Izumikawa Pieter, Mestdagh Denis, Lafontaine L.J. Gaetano, Tartaglia Gian Nobuhiro, Takahashi Jean-Christophe, Marine Eleonora, Leucci Nat Struct Mol Biol Article Synchronisation of translation rates between the mitochondria and their cellular host is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translation uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, the compensating mechanisms in place in the mitochondria remain elusive. Here we show that the malignant lncRNA SAMMSON promotes a balanced increase in rRNA maturation and protein synthesis in the cytosol and mitochondria by modulating the localisation of CARF, an RNA-binding protein sequestering XRN2 in the nucleoplasm and limiting nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favouring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. This data highlights how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth. 2018-10-29 2018-11 /pmc/articles/PMC6223542/ /pubmed/30374086 http://dx.doi.org/10.1038/s41594-018-0143-4 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Roberto, Vendramin
Yvessa, Verheyden
Hideaki, Ishikawa
Lucas, Goedert
Emilien, Nicolas
Kritika, Saraf
Alexandros, Armaos
Riccardo, Delli Ponti
Keiichi, Izumikawa
Pieter, Mestdagh
Denis, Lafontaine L.J.
Gaetano, Tartaglia Gian
Nobuhiro, Takahashi
Jean-Christophe, Marine
Eleonora, Leucci
SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title_full SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title_fullStr SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title_full_unstemmed SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title_short SAMMSON fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
title_sort sammson fosters cancer cell fitness by enhancing concertedly mitochondrial and cytosolic translation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223542/
https://www.ncbi.nlm.nih.gov/pubmed/30374086
http://dx.doi.org/10.1038/s41594-018-0143-4
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