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

Roberto Vendramin, Yvessa Verheyden, Hideaki Ishikawa, Lucas Goedert, Emilien Nicolas, Kritika Saraf, Alexandros Armaos, Riccardo Delli Ponti, Keichi Izumikawa, Pieter Mestdagh, Denis L J Lafontaine, Gian Gaetano Tartaglia, Nobuhiro Takahashi, Jean-Christophe Marine, Eleonora Leucci

Research output: Contribution to journalArticlepeer-review

Abstract

Synchronization of mitochondrial and cytoplasmic translation rates is critical for the maintenance of cellular fitness, with cancer cells being especially vulnerable to translational uncoupling. Although alterations of cytosolic protein synthesis are common in human cancer, compensating mechanisms in mitochondrial translation remain elusive. Here we show that the malignant long non-coding RNA (lncRNA) SAMMSON promotes a balanced increase in ribosomal RNA (rRNA) maturation and protein synthesis in the cytosol and mitochondria by modulating the localization of CARF, an RNA-binding protein that sequesters the exo-ribonuclease XRN2 in the nucleoplasm, which under normal circumstances limits nucleolar rRNA maturation. SAMMSON interferes with XRN2 binding to CARF in the nucleus by favoring the formation of an aberrant cytoplasmic RNA-protein complex containing CARF and p32, a mitochondrial protein required for the processing of the mitochondrial rRNAs. These data highlight how a single oncogenic lncRNA can simultaneously modulate RNA-protein complex formation in two distinct cellular compartments to promote cell growth.

Original languageEnglish
Pages (from-to)1035-1046
Number of pages12
JournalNature structural & molecular biology
Volume25
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018
Externally publishedYes

Keywords

  • Apoptosis Regulatory Proteins/metabolism
  • Binding Sites
  • Cell Compartmentation
  • Cell Line, Tumor
  • Cell Nucleus/metabolism
  • Cell Proliferation/genetics
  • Cytosol/metabolism
  • Exoribonucleases/metabolism
  • HEK293 Cells
  • Humans
  • Mitochondria/metabolism
  • Models, Biological
  • Neoplasms/genetics
  • Protein Biosynthesis/genetics
  • RNA Processing, Post-Transcriptional
  • RNA, Long Noncoding/genetics
  • RNA, Ribosomal/genetics
  • RNA-Binding Proteins/metabolism

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