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ORIGINAL RESEARCH article

Front. Immunol.
Sec. T Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1415839

The nuclear GYF protein CD2BP2/U5-52K is required for T cell homeostasis

Provisionally accepted
Christian Freund Christian Freund 1*Miriam Bertazzon Miriam Bertazzon 1Almudena Hurtado-Pico Almudena Hurtado-Pico 1Carlos Plaza-Sirvent Carlos Plaza-Sirvent 2Marc Schuster Marc Schuster 3Marco Preußner Marco Preußner 1Miguel Alvaro-Benito Miguel Alvaro-Benito 1Esam Abualrous Esam Abualrous 1Gesa I. Albert Gesa I. Albert 4Florian Heyd Florian Heyd 1Stefanie Kliche Stefanie Kliche 5Ingo Schmitz Ingo Schmitz 2
  • 1 Free University of Berlin, Berlin, Germany
  • 2 Ruhr University Bochum, Bochum, North Rhine-Westphalia, Germany
  • 3 Miltenyi Biotec, Bergisch Gladbach, North Rhine-Westphalia, Germany
  • 4 Roche Diagnostics International Ltd, Free University of Berlin, Berlin, Germany
  • 5 Otto von Guericke University Magdeburg, Magdeburg, Saxony-Anhalt, Germany

The final, formatted version of the article will be published soon.

    The question whether interference with the ubiquitous splicing machinery can lead to cell-type specific perturbation of cellular function is addressed here by T cell specific ablation of the general U5 snRNP assembly factor CD2BP2/U5-52K. This protein defines the family of nuclear GYF domain containing proteins that are ubiquitously expressed in eukaryotes with essential functions ascribed to early embryogenesis and organ function. Abrogating CD2BP2/U5-52K in T cells, allows us to delineate the consequences of splicing machinery interferences for T cell development and function. Increased T cell lymphopenia and T cell death are observed upon depletion of CD2BP2/U5-52K. A substantial increase in exon skipping coincides with the observed defect in the proliferation/differentiation balance in the absence of CD2BP2/U5-52K. Prominently, skipping of exon 7 in Mdm4 is observed, coinciding with upregulation of pro-apoptotic gene expression profiles upon CD2BP2/U5-52K depletion. Furthermore, we observe enhanced sensitivity of naïve T cells compared to memory T cells to changes in CD2BP2/U5-52K levels, indicating that that depletion of this general splicing factor leads to modulation of T cell homeostasis.

    Keywords: CD2BP2/U5-15K, T cell, spliceosome, Mdm4, p53, exon skipping

    Received: 11 Apr 2024; Accepted: 11 Jul 2024.

    Copyright: © 2024 Freund, Bertazzon, Hurtado-Pico, Plaza-Sirvent, Schuster, Preußner, Alvaro-Benito, Abualrous, Albert, Heyd, Kliche and Schmitz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Christian Freund, Free University of Berlin, Berlin, Germany

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