Nonclassical nuclear localization signals mediate nuclear import of CIRBP

Publication type:
Journal article
Metadata:
Autoren
  • Benjamin Bourgeois
  • Saskia Hutten
  • Benjamin Gottschalk
  • Mario Hofweber
  • Gesa Richter
  • Julia Sternat
  • Claudia Abou-Ajram
  • Christoph Goebl
  • Gerd Leitinger
  • Wolfgang F Graier
  • Dorothee Dormann
  • Tobias Madl
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000526871700043&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1073/pnas.1918944117
Externe Identifier
  • Clarivate Analytics Document Solution ID: LE6ZF
  • PubMed Identifier: 32234784
ISSN
0027-8424
Ausgabe der Veröffentlichung
15
Zeitschrift
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Schlüsselwörter
  • CIRBP
  • Transportin-1
  • Transportin-3
  • nuclear import
  • phase separation
Paginierung
8503 - 8514
Datum der Veröffentlichung
2020
Status
Published
Titel
Nonclassical nuclear localization signals mediate nuclear import of CIRBP
Sub types
  • Article
Ausgabe der Zeitschrift
117

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Significance</jats:title> <jats:p>We uncovered a molecular mechanism by which multiple importins regulate nuclear import, phase separation, and stress granule recruitment of an RNA-binding protein. Our work permitted the identification of two types of nuclear localization signal (NLS) in cold-inducible RNA-binding protein (CIRBP). We show that CIRBP, which lacks any classical NLS, binds both the importin Transportin-1 (TNPO1) and Transportin-3 (TNPO3). These interactions and nuclear import of CIRBP involve two distinct CIRBP regions, the arginine-glycine(-glycine) (RG/RGG) region and the discovered arginine-serine-tyrosine (RSY)–rich region. We show that these two regions harbor different specificity toward TNPO1 and TNPO3, with the RG/RGG-NLS being specialized in TNPO1 recognition and the RSY-NLS being specialized in TNPO3 recognition.</jats:p>
Autoren
  • Benjamin Bourgeois
  • Saskia Hutten
  • Benjamin Gottschalk
  • Mario Hofweber
  • Gesa Richter
  • Julia Sternat
  • Claudia Abou-Ajram
  • Christoph Göbl
  • Gerd Leitinger
  • Wolfgang F Graier
  • Dorothee Dormann
  • Tobias Madl
DOI
10.1073/pnas.1918944117
eISSN
1091-6490
ISSN
0027-8424
Ausgabe der Veröffentlichung
15
Zeitschrift
Proceedings of the National Academy of Sciences
Sprache
en
Online publication date
2020
Paginierung
8503 - 8514
Datum der Veröffentlichung
2020
Status
Published
Herausgeber
Proceedings of the National Academy of Sciences
Herausgeber URL
http://dx.doi.org/10.1073/pnas.1918944117
Datum der Datenerfassung
2022
Titel
Nonclassical nuclear localization signals mediate nuclear import of CIRBP
Ausgabe der Zeitschrift
117

Data source: Crossref

Abstract
The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.
Addresses
  • Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology & Biochemistry, Medical University of Graz, 8010 Graz, Austria.
Autoren
  • Benjamin Bourgeois
  • Saskia Hutten
  • Benjamin Gottschalk
  • Mario Hofweber
  • Gesa Richter
  • Julia Sternat
  • Claudia Abou-Ajram
  • Christoph Göbl
  • Gerd Leitinger
  • Wolfgang F Graier
  • Dorothee Dormann
  • Tobias Madl
DOI
10.1073/pnas.1918944117
eISSN
1091-6490
Externe Identifier
  • PubMed Identifier: 32234784
  • PubMed Central ID: PMC7165476
Funding acknowledgements
  • Austrian Science Fund FWF: I 3792
  • Austrian Science Fund FWF: W 1226-B18
  • Austrian Science Fund FWF: W 1226
  • Austrian Science Fund FWF: P 28854
Open access
true
ISSN
0027-8424
Ausgabe der Veröffentlichung
15
Zeitschrift
Proceedings of the National Academy of Sciences of the United States of America
Schlüsselwörter
  • Hela Cells
  • Cell Nucleus
  • Cytoplasm
  • Humans
  • Arginine
  • Tyrosine
  • Serine
  • Glycine
  • Peptide Fragments
  • beta Karyopherins
  • RNA-Binding Proteins
  • Protein Conformation
  • Protein Binding
  • Active Transport, Cell Nucleus
  • Nuclear Localization Signals
Sprache
eng
Medium
Print-Electronic
Online publication date
2020
Open access status
Open Access
Paginierung
8503 - 8514
Datum der Veröffentlichung
2020
Status
Published
Publisher licence
CC BY-NC-ND
Datum der Datenerfassung
2020
Titel
Nonclassical nuclear localization signals mediate nuclear import of CIRBP.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
117

Files

https://www.pnas.org/content/pnas/117/15/8503.full.pdf https://europepmc.org/articles/PMC7165476?pdf=render

Data source: Europe PubMed Central

Abstract
The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.
Autoren
  • Benjamin Bourgeois
  • Saskia Hutten
  • Benjamin Gottschalk
  • Mario Hofweber
  • Gesa Richter
  • Julia Sternat
  • Claudia Abou-Ajram
  • Christoph Göbl
  • Gerd Leitinger
  • Wolfgang F Graier
  • Dorothee Dormann
  • Tobias Madl
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/32234784
DOI
10.1073/pnas.1918944117
eISSN
1091-6490
Externe Identifier
  • PubMed Central ID: PMC7165476
Funding acknowledgements
  • Austrian Science Fund FWF: I 3792
  • Austrian Science Fund FWF: P 28854
  • Austrian Science Fund FWF: W 1226
Ausgabe der Veröffentlichung
15
Zeitschrift
Proc Natl Acad Sci U S A
Schlüsselwörter
  • CIRBP
  • Transportin-1
  • Transportin-3
  • nuclear import
  • phase separation
  • Active Transport, Cell Nucleus
  • Arginine
  • Cell Nucleus
  • Cytoplasm
  • Glycine
  • HeLa Cells
  • Humans
  • Nuclear Localization Signals
  • Peptide Fragments
  • Protein Binding
  • Protein Conformation
  • RNA-Binding Proteins
  • Serine
  • Tyrosine
  • beta Karyopherins
Sprache
eng
Country
United States
Paginierung
8503 - 8514
PII
1918944117
Datum der Veröffentlichung
2020
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Titel
Nonclassical nuclear localization signals mediate nuclear import of CIRBP.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
117

Data source: PubMed

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