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Tnpo3 控制编码 iNKT 细胞典型 TCR α 链前体 mRNA 的剪接。

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

机构信息

Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.

Center for Bioscience Research and Education, Utsunomiya University, Utsunomiya, Tochigi, 321-8505, Japan.

出版信息

Nat Commun. 2023 Jun 20;14(1):3645. doi: 10.1038/s41467-023-39422-4.

DOI:10.1038/s41467-023-39422-4
PMID:37339974
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10282035/
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.

摘要

非传统 T 细胞，如先天自然杀伤 T 细胞（iNKT）细胞，是脊椎动物免疫防御的重要组成部分。iNKT 通过由半不变 TCRα 链与一组受限的 TCRβ 链组成的 T 细胞受体（TCR）识别糖脂。在这里，我们表明编码该半不变 TCR 特征性 Vα14Jα18 可变区的同源 Trav11-Traj18-Trac 前体 mRNA 的剪接依赖于 Tnpo3 的存在。Tnpo3 基因编码 β-核孔蛋白家族的核转运蛋白，其货物包括各种剪接调节剂。在缺乏 Tnpo3 的情况下，iNKT 细胞发育受阻可以通过转基因提供重排的 Trav11-Traj18-Trac cDNA 来克服，这表明 Tnpo3 缺乏本身并不干扰 iNKT 细胞的发育。因此，我们的研究确定了 Tnpo3 在调节 iNKT 细胞的同源 TCRα 链前体 mRNA 剪接中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/935137a1e375/41467_2023_39422_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/844f04a6b506/41467_2023_39422_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/9e034fbd5d9d/41467_2023_39422_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/e9d1bb5c3c78/41467_2023_39422_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/8cf794619957/41467_2023_39422_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/2331089b94c9/41467_2023_39422_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/935137a1e375/41467_2023_39422_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/844f04a6b506/41467_2023_39422_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/9e034fbd5d9d/41467_2023_39422_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/e9d1bb5c3c78/41467_2023_39422_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/8cf794619957/41467_2023_39422_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/2331089b94c9/41467_2023_39422_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d653/10282035/935137a1e375/41467_2023_39422_Fig6_HTML.jpg

相似文献

[1]
Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR α chain of iNKT cells.

Nat Commun. 2023-6-20

[2]
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[3]
Mutation of the Traj18 gene segment using TALENs to generate Natural Killer T cell deficient mice.

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[4]
Effective functional maturation of invariant natural killer T cells is constrained by negative selection and T-cell antigen receptor affinity.

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[5]
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Immunol Cell Biol. 2016-9

[6]
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[7]
Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.

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[8]
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[9]
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[10]
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引用本文的文献

[1]
Precursor RNA structural patterns at SF3B1 mutation sensitive cryptic 3' splice sites.

bioRxiv. 2025-2-22

本文引用的文献

[1]
SRSF1 plays a critical role in invariant natural killer T cell development and function.

Cell Mol Immunol. 2021-11

[2]
Thymic iNKT single cell analyses unmask the common developmental program of mouse innate T cells.

Nat Commun. 2020-12-7

[3]
Single-cell RNA sequencing identifies shared differentiation paths of mouse thymic innate T cells.

Nat Commun. 2020-8-31

[4]
Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge.

Nat Rev Immunol. 2020-12

[5]
Recent advances in iNKT cell development.

F1000Res. 2020-2-20

[6]
Modeling RNA-Binding Protein Specificity In Vivo by Precisely Registering Protein-RNA Crosslink Sites.

Mol Cell. 2019-6-20

[7]
Nonsense-mediated mRNA decay: The challenge of telling right from wrong in a complex transcriptome.

Wiley Interdiscip Rev RNA. 2019-5-26

[8]
How Lipid-Specific T Cells Become Effectors: The Differentiation of iNKT Subsets.

Front Immunol. 2018-6-26

[9]
TCR signal strength controls thymic differentiation of iNKT cell subsets.

Nat Commun. 2018-7-9

[10]
Invariant Natural Killer T Cell Subsets-More Than Just Developmental Intermediates.

Front Immunol. 2018-6-20

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