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

Abstract

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 Lab. (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. 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., 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. doi: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 = {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 = {2016},
month = {2}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.7554/eLife.13571

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Cited by: 33 works
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