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

Norimasa Iwanami, Andreas S. Richter, Katarzyna Sikora and Thomas Boehm ()
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Norimasa Iwanami: Max Planck Institute of Immunobiology and Epigenetics
Andreas S. Richter: Max Planck Institute of Immunobiology and Epigenetics
Katarzyna Sikora: Max Planck Institute of Immunobiology and Epigenetics
Thomas Boehm: Max Planck Institute of Immunobiology and Epigenetics

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract 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 α chain, paired with a restricted set of TCR β chains. Here, we show that splicing of the cognate Trav11-Traj18-Trac pre-mRNA encoding the characteristic Vα14Jα18 variable region of this semi-invariant TCR depends on the presence of Tnpo3. The Tnpo3 gene encodes a nuclear transporter of the β-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 TCRα chain of iNKT cells.

Date: 2023
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DOI: 10.1038/s41467-023-39422-4

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