Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells
The RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and pro...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2022
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| _version_ | 1797109626554023936 |
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| author | D'Angeli, V Monzón-Casanova, E Matheson, LS Gizlenci, Ö Petkau, G Gooding, C Berrens, RV Smith, CWJ Turner, M |
| author_facet | D'Angeli, V Monzón-Casanova, E Matheson, LS Gizlenci, Ö Petkau, G Gooding, C Berrens, RV Smith, CWJ Turner, M |
| author_sort | D'Angeli, V |
| collection | OXFORD |
| description | The RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ∼200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2, and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter Aβ1 isoform and exon 13 skipped Aβ2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T-cell activation. |
| first_indexed | 2024-03-07T07:44:10Z |
| format | Journal article |
| id | oxford-uuid:9214c795-38b5-4bbd-a463-bc89f38f2f11 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:44:10Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:9214c795-38b5-4bbd-a463-bc89f38f2f112023-05-19T14:36:31ZPolypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cellsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9214c795-38b5-4bbd-a463-bc89f38f2f11EnglishSymplectic ElementsWiley2022D'Angeli, VMonzón-Casanova, EMatheson, LSGizlenci, ÖPetkau, GGooding, CBerrens, RVSmith, CWJTurner, MThe RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ∼200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2, and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter Aβ1 isoform and exon 13 skipped Aβ2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T-cell activation. |
| spellingShingle | D'Angeli, V Monzón-Casanova, E Matheson, LS Gizlenci, Ö Petkau, G Gooding, C Berrens, RV Smith, CWJ Turner, M Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title | Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title_full | Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title_fullStr | Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title_full_unstemmed | Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title_short | Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells |
| title_sort | polypyrimidine tract binding protein 1 regulates the activation of mouse cd8 t cells |
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