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

Author

Listed:
  • Norimasa Iwanami

    (Max Planck Institute of Immunobiology and Epigenetics
    Utsunomiya University, Utsunomiya)

  • Andreas S. Richter

    (Max Planck Institute of Immunobiology and Epigenetics
    Genedata AG)

  • Katarzyna Sikora

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Thomas Boehm

    (Max Planck Institute of Immunobiology and Epigenetics
    Albert Ludwigs University)

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.

Suggested Citation

  • Norimasa Iwanami & Andreas S. Richter & Katarzyna Sikora & Thomas Boehm, 2023. "Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR α chain of iNKT cells," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39422-4
    DOI: 10.1038/s41467-023-39422-4
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    1. Yuki Kinjo & Douglass Wu & Gisen Kim & Guo-Wen Xing & Michael A. Poles & David D. Ho & Moriya Tsuji & Kazuyoshi Kawahara & Chi-Huey Wong & Mitchell Kronenberg, 2005. "Recognition of bacterial glycosphingolipids by natural killer T cells," Nature, Nature, vol. 434(7032), pages 520-525, March.
    2. Jochen Mattner & Kristin L. DeBord & Nahed Ismail & Randal D. Goff & Carlos Cantu & Dapeng Zhou & Pierre Saint-Mezard & Vivien Wang & Ying Gao & Ning Yin & Kasper Hoebe & Olaf Schneewind & David Walke, 2005. "Exogenous and endogenous glycolipid antigens activate NKT cells during microbial infections," Nature, Nature, vol. 434(7032), pages 525-529, March.
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