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dc.contributor.authorMonzón-Casanova, Elisa
dc.contributor.authorMatheson, Louise S
dc.contributor.authorTabbada, Kristina
dc.contributor.authorZarnack, Kathi
dc.contributor.authorSmith, Christopher WJ
dc.contributor.authorTurner, Martin
dc.date.accessioned2020-03-06T05:05:57Z
dc.date.available2020-03-06T05:05:57Z
dc.date.issued2020-02-21
dc.date.submitted2019-11-13
dc.identifier.other53557
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/303098
dc.description.abstractPolypyrimidine 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.
dc.languageen
dc.publishereLife Sciences Publications, Ltd
dc.subjectResearch Article
dc.subjectChromosomes and Gene Expression
dc.subjectImmunology and Inflammation
dc.subjectB cell development
dc.subjectRNA-binding proteins
dc.subjectalternative splicing
dc.subjectcell cycle
dc.subjectMouse
dc.titlePolypyrimidine tract-binding proteins are essential for B cell development
dc.typeArticle
dc.date.updated2020-03-06T05:05:55Z
prism.publicationNameeLife
prism.volume9
dc.identifier.doi10.17863/CAM.50175
dcterms.dateAccepted2020-02-20
rioxxterms.versionofrecord10.7554/elife.53557
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Black, Douglas L
datacite.contributor.supervisorsenior_editor: Manley, James L
dc.contributor.orcidMonzón-Casanova, Elisa [0000-0001-6617-6138]
dc.contributor.orcidZarnack, Kathi [0000-0003-3527-3378]
dc.contributor.orcidSmith, Christopher WJ [0000-0002-2753-3398]
dc.contributor.orcidTurner, Martin [0000-0002-3801-9896]
dc.identifier.eissn2050-084X
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/J00152X/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/P01898X/1)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BBS/E/B/000C0407)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BBS/E/B/000C0427)
pubs.funder-project-idWellcome (200823/Z/16/Z)
pubs.funder-project-idEuropean Cooperation in Science and Technology (CA17103)
pubs.funder-project-idGerman Research Foundation (ZA 881/2-1)


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