Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA

The nucleolus is a membrane-less organelle formed through liquid-liquid phase separation of its components from the surrounding nucleoplasm. Here, we show that nucleophosmin (NPM1) integrates within the nucleolus via a multi-modal mechanism involving multivalent interactions with proteins containing arginine-rich linear motifs (R-motifs) and ribosomal RNA (rRNA). Importantly, these R-motifs are found in canonical nucleolar localization signals. Based on a novel combination of biophysical approaches, we propose a model for the molecular organization within liquid-like droplets formed by the N-terminal domain of NPM1 and R-motif peptides, thus providing insights into the structural organization of the nucleolus.…

• UD
  U.S. Department of Energy
• AL
  American Lebanese Syrian Associated Charities
• NI
  National Institutes of Health

  Award: R01CA082491
• NC
  National Cancer Institute

  Award: P30CA21765
• NI
  National Institute of General Medical Sciences

  Awards: 1R01GM083159, F32GM113290, 1R01GM115634, R01GM066833