Selected Publication:
SHR
Neuro
Cancer
Cardio
Lipid
Metab
Microb
Zhou, Q; Sagmeister, T; Hutten, S; Bourgeois, B; Pavkov-Keller, T; Dormann, D; Madl, T.
Structural basis of phosphorylation-independent nuclear import of CIRBP by TNPO3.
Nat Commun. 2025; 16(1):4456
Doi: 10.1038/s41467-025-59802-2
[OPEN ACCESS]
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
-
Madl Tobias
-
Zhou Qishun
- Co-authors Med Uni Graz
-
Bourgeois Benjamin Michel Rene
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Transportin 3 (TNPO3) is a nuclear import receptor known for its broad substrate specificity, often recognizing arginine-serine (SR/RS) repeat-rich nuclear localization signals (NLS) in SRSF proteins. While serine phosphorylation or glutamate presence has been associated with these NLSs, recent proteomic studies identified TNPO3 cargoes lacking SR/RS repeats. One such example is the cold-inducible RNA-binding protein (CIRBP), which contains a non-classical RSY-NLS. Using X-ray crystallography, here we investigate the TNPO3-CIRBP interaction and find that tyrosines within the RSY-NLS play a key role in binding, independent of phosphorylation. Surprisingly, serine and tyrosine phosphorylation in CIRBP's NLS inhibits TNPO3 binding, suggesting a regulatory mechanism for nuclear import. Our study reveals a non-conventional nuclear import mechanism mediated by TNPO3, which may extend to other known or yet undiscovered TNPO3 cargoes.
- Find related publications in this database (using NLM MeSH Indexing)
-
Phosphorylation - administration & dosage
-
RNA-Binding Proteins - metabolism, chemistry, genetics
-
Active Transport, Cell Nucleus - administration & dosage
-
Humans - administration & dosage
-
Crystallography, X-Ray - administration & dosage
-
beta Karyopherins - metabolism, chemistry, genetics
-
Nuclear Localization Signals - metabolism
-
Protein Binding - administration & dosage
-
Cell Nucleus - metabolism
-
Tyrosine - metabolism
-
Models, Molecular - administration & dosage