Polypyrimidine tract-binding proteins are essential for B cell development
Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of bot...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/53557 |
| _version_ | 1811180689949720576 |
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| author | Elisa Monzón-Casanova Louise S Matheson Kristina Tabbada Kathi Zarnack Christopher WJ Smith Martin Turner |
| author_facet | Elisa Monzón-Casanova Louise S Matheson Kristina Tabbada Kathi Zarnack Christopher WJ Smith Martin Turner |
| author_sort | Elisa Monzón-Casanova |
| collection | DOAJ |
| description | Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle. |
| first_indexed | 2024-04-11T09:07:31Z |
| format | Article |
| id | doaj.art-b68b2bc2ff684844afe3e2ee6dd99ca4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:07:31Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-b68b2bc2ff684844afe3e2ee6dd99ca42022-12-22T04:32:35ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.53557Polypyrimidine tract-binding proteins are essential for B cell developmentElisa Monzón-Casanova0https://orcid.org/0000-0001-6617-6138Louise S Matheson1Kristina Tabbada2Kathi Zarnack3https://orcid.org/0000-0003-3527-3378Christopher WJ Smith4https://orcid.org/0000-0002-2753-3398Martin Turner5https://orcid.org/0000-0002-3801-9896Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom; Department of Biochemistry, University of Cambridge, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United KingdomNext Generation Sequencing Facility, The Babraham Institute, Cambridge, United KingdomBuchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, GermanyDepartment of Biochemistry, University of Cambridge, Cambridge, United KingdomLaboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United KingdomPolypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle.https://elifesciences.org/articles/53557B cell developmentRNA-binding proteinsalternative splicingcell cycle |
| spellingShingle | Elisa Monzón-Casanova Louise S Matheson Kristina Tabbada Kathi Zarnack Christopher WJ Smith Martin Turner Polypyrimidine tract-binding proteins are essential for B cell development eLife B cell development RNA-binding proteins alternative splicing cell cycle |
| title | Polypyrimidine tract-binding proteins are essential for B cell development |
| title_full | Polypyrimidine tract-binding proteins are essential for B cell development |
| title_fullStr | Polypyrimidine tract-binding proteins are essential for B cell development |
| title_full_unstemmed | Polypyrimidine tract-binding proteins are essential for B cell development |
| title_short | Polypyrimidine tract-binding proteins are essential for B cell development |
| title_sort | polypyrimidine tract binding proteins are essential for b cell development |
| topic | B cell development RNA-binding proteins alternative splicing cell cycle |
| url | https://elifesciences.org/articles/53557 |
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