BRCA1-Dependent Translational Regulation in Breast Cancer Cells

PLoS One. 2013 Jun 21;8(6):e67313. doi: 10.1371/journal.pone.0067313. Print 2013.

Abstract

BRCA1 (Breast Cancer 1) has been implicated in a number of cellular processes, including transcription regulation, DNA damage repair and protein ubiquitination. We previously demonstrated that BRCA1 interacts with PABP1 (Poly(A)-Binding Protein 1) and that BRCA1 modulates protein synthesis through this interaction. To identify the mRNAs that are translationally regulated by BRCA1, we used a microarray analysis of polysome-bound mRNAs in BRCA1-depleted and non-depleted MCF7 cells. Our findings show that BRCA1 modifies the translational efficiency of approximately 7% of the mRNAs expressed in these cells. Further analysis revealed that several processes contributing to cell surveillance such as cell cycle arrest, cell death, cellular growth and proliferation, DNA repair and gene expression, are largely enriched for the mRNAs whose translation is impacted by BRCA1. The BRCA1-dependent translation of these species of mRNAs therefore uncovers a novel mechanism through which BRCA1 exerts its onco-suppressive role. In addition, the BRCA1-dependent translation of mRNAs participating in unexpected functions such as cellular movement, nucleic acid metabolism or protein trafficking is indicative of novel functions for BRCA1. Finally, this study contributes to the identification of several markers associated with BRCA1 deficiency and to the discovery of new potential anti-neoplastic therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Female
  • Humans
  • MCF-7 Cells
  • Poly(A)-Binding Protein I / genetics
  • Poly(A)-Binding Protein I / metabolism*
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Biomarkers, Tumor
  • Poly(A)-Binding Protein I
  • RNA, Messenger
  • RNA, Neoplasm

Grants and funding

This work was supported by the ‘Institut National contre le Cancer’ (INCa) (RIBOCAN), the ‘Ligue Nationale Contre le Cancer’(LNCC) (Equipe labellisée 2008), the ‘Association pour la Recherche sur le Cancer’ (ARC) and the ‘Electricité de France’ (EDF) (Commission de Radioprotection). ED is supported by a fellowship from the French Ministry of Research and from the Université Lyon 1 (Attaché Temporaire d’Enseignement et de Recherche). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors‚ adherence to all the PLOS ONE policies on sharing data and materials.