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. |