TY - JOUR
T1 - The glycine arginine-rich domain of the RNA-binding protein nucleolin regulates its subcellular localization
AU - Doron, Ella
AU - Koppel, Indrek
AU - Abraham, Ofri
AU - Rishal, Ida
AU - Smith, Terika P
AU - Buchanan, Courtney N
AU - Sahoo, Pabitra K
AU - Oses-Prieto, Juan A.
AU - Kawaguchi, Riki
AU - Alber, Stefanie
AU - Zahavi, Eitan Erez
AU - Di Matteo, Pierluigi
AU - Di Pizio, Agostina
AU - Song, Didi Andreas
AU - Okladnikova, Nataliya
AU - Gordon, Dalia
AU - Ben-Dor, Shifra
AU - Haffner-Krausz, Rebecca
AU - Coppola, Giovanni
AU - Burlingame, Alma L.
AU - Jungwirth, Pavel
AU - Twiss, Jeffery L.
AU - Fainzilber, Michael
N1 - We sincerely thank Andres Ramos (University College London) for valuable insights, Vladimir Kiss, and Reinat Nevo for assistance with microscopy; Yael Fridmann‐Sirkis for assistance with surface plasmon resonance; and Yarden Tzur, Rotem Perry, and Avraham Yaron for helpful discussions. We gratefully acknowledge funding from the Israel Science Foundation (ISF 1337/18 to MF), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to GC, ALB, JLT & MF), the National Institutes of Health (K01NS105879 to TPS, R01NS117821 and R01NS089633 to JLT, P41GM103481, and 1S10OD016229 to ALB), the South Carolina Spinal Cord Injury Research Fund (2019 PD‐02 to PKS), and the Czech Science Foundation (EXPRO 19‐26854X to PJ).
PY - 2021/10/18
Y1 - 2021/10/18
N2 - Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.
AB - Nucleolin is a multifunctional RNA Binding Protein (RBP) with diverse subcellular localizations, including the nucleolus in all eukaryotic cells, the plasma membrane in tumor cells, and the axon in neurons. Here we show that the glycine arginine rich (GAR) domain of nucleolin drives subcellular localization via protein-protein interactions with a kinesin light chain. In addition, GAR sequences mediate plasma membrane interactions of nucleolin. Both these modalities are in addition to the already reported involvement of the GAR domain in liquid-liquid phase separation in the nucleolus. Nucleolin transport to axons requires the GAR domain, and heterozygous GAR deletion mice reveal reduced axonal localization of nucleolin cargo mRNAs and enhanced sensory neuron growth. Thus, the GAR domain governs axonal transport of a growth controlling RNA-RBP complex in neurons, and is a versatile localization determinant for different subcellular compartments. Localization determination by GAR domains may explain why GAR mutants in diverse RBPs are associated with neurodegenerative disease.
UR - http://www.scopus.com/inward/record.url?scp=85114717476&partnerID=8YFLogxK
U2 - 10.15252/embj.2020107158
DO - 10.15252/embj.2020107158
M3 - مقالة
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 20
M1 - e107158
ER -