Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA
Abstract
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.
- Authors:
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1239698
- Alternate Identifier(s):
- OSTI ID: 1239699; OSTI ID: 1241461
- Grant/Contract Number:
- AC05-00OR22725; TGIR-RMN-00625
- Resource Type:
- Published Article
- Journal Name:
- eLife
- Additional Journal Information:
- Journal Name: eLife Journal Volume: 5; Journal ID: ISSN 2050-084X
- Publisher:
- eLife Sciences Publications, Ltd.
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Mitrea, Diana M., Cika, Jaclyn A., Guy, Clifford S., Ban, David, Banerjee, Priya R., Stanley, Christopher B., Nourse, Amanda, Deniz, Ashok A., and Kriwacki, Richard W. Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA. United States: N. p., 2016.
Web. doi:10.7554/eLife.13571.
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. Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA. United States. https://doi.org/10.7554/eLife.13571
Mitrea, Diana M., Cika, Jaclyn A., Guy, Clifford S., Ban, David, Banerjee, Priya R., Stanley, Christopher B., Nourse, Amanda, Deniz, Ashok A., and Kriwacki, Richard W. Tue .
"Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA". United States. https://doi.org/10.7554/eLife.13571.
@article{osti_1239698,
title = {Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA},
author = {Mitrea, Diana M. and Cika, Jaclyn A. and Guy, Clifford S. and Ban, David and Banerjee, Priya R. and Stanley, Christopher B. and Nourse, Amanda and Deniz, Ashok A. and Kriwacki, Richard W.},
abstractNote = {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.},
doi = {10.7554/eLife.13571},
journal = {eLife},
number = ,
volume = 5,
place = {United States},
year = {Tue Feb 02 00:00:00 EST 2016},
month = {Tue Feb 02 00:00:00 EST 2016}
}
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