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Publication : Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR α chain of iNKT cells.

First Author  Iwanami N Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  3645
PubMed ID  37339974 Mgi Jnum  J:337059
Mgi Id  MGI:7492835 Doi  10.1038/s41467-023-39422-4
Citation  Iwanami N, et al. (2023) Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR alpha chain of iNKT cells. Nat Commun 14(1):3645
abstractText  Unconventional T cells, such as innate natural killer T cells (iNKT) cells, are an important part of vertebrate immune defences. iNKT recognise glycolipids through a T cell receptor (TCR) that is composed of a semi-invariant TCR alpha chain, paired with a restricted set of TCR beta chains. Here, we show that splicing of the cognate Trav11-Traj18-Trac pre-mRNA encoding the characteristic Valpha14Jalpha18 variable region of this semi-invariant TCR depends on the presence of Tnpo3. The Tnpo3 gene encodes a nuclear transporter of the beta-karyopherin family whose cargo includes various splice regulators. The block of iNKT cell development in the absence of Tnpo3 can be overcome by transgenic provision of a rearranged Trav11-Traj18-Trac cDNA, indicating that Tnpo3 deficiency does not interfere with the development of iNKT cells per se. Our study thus identifies a role for Tnpo3 in regulating the splicing of the pre-mRNA encoding the cognate TCRalpha chain of iNKT cells.
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