Author
Listed:
- Qishun Zhou
(Medical University of Graz
Institut Pasteur, Université Paris Cité, CNRS UMR3528, Bacterial Transmembrane Systems Unit)
- Theo Sagmeister
(University of Graz)
- Saskia Hutten
(Institute of Molecular Physiology)
- Benjamin Bourgeois
(Medical University of Graz)
- Tea Pavkov-Keller
(University of Graz
University of Graz
BioTechMed-Graz)
- Dorothee Dormann
(Institute of Molecular Physiology
Institute of Molecular Biology (IMB) Mainz)
- Tobias Madl
(Medical University of Graz
BioTechMed-Graz)
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.
Suggested Citation
Qishun Zhou & Theo Sagmeister & Saskia Hutten & Benjamin Bourgeois & Tea Pavkov-Keller & Dorothee Dormann & Tobias Madl, 2025.
"Structural basis of phosphorylation-independent nuclear import of CIRBP by TNPO3,"
Nature Communications, Nature, vol. 16(1), pages 1-14, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59802-2
DOI: 10.1038/s41467-025-59802-2
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