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 - Kadlec, Jan
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
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 - Article
SN - 0261-4189
VL - 40
JO - EMBO Journal
JF - EMBO Journal
IS - 20
M1 - e107158
ER -