Medizinische Universität Graz - Research portal

Logo MUG Resarch Portal

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 PUBMED Central 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

© Med Uni GrazImprint