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

Mitrea, Diana M.; Cika, Jaclyn A.; Guy, Clifford S.; Ban, David; Banerjee, Priya R.; Stanley, Christopher B.; Nourse, Amanda; Deniz, Ashok A.; Kriwacki, Richard W.

doi:10.7554/eLife.13571

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

Journal Article · Tue Feb 02 00:00:00 EST 2016 · eLife

DOI:https://doi.org/10.7554/eLife.13571· OSTI ID:1239698

Mitrea, Diana M.; Cika, Jaclyn A.; Guy, Clifford S.; Ban, David; Banerjee, Priya R.; Stanley, Christopher B.; Nourse, Amanda; Deniz, Ashok A.; Kriwacki, Richard W.

In this study, 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. We identify multivalency of acidic tracts and folded nucleic acid binding domains, mediated by N-terminal domain oligomerization, as structural features required for phase separation of NPM1 with other nucleolar components in vitro and for localization within mammalian nucleoli. We propose that one mechanism of nucleolar localization involves phase separation of proteins within the nucleolus.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC05-00OR22725; TGIR-RMN-00625

OSTI ID:: 1239698

Alternate ID(s):: OSTI ID: 1239699; OSTI ID: 1241461

Journal Information:: eLife, Journal Name: eLife Vol. 5; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 299 works

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