Nature Immunology 7, 859 - 867 (2006)
Published online: 2 July 2006; | doi:10.1038/ni1361
Auxiliary splice factor U2AF26 and transcription factor Gfi1 cooperate directly in regulating CD45 alternative splicingFlorian Heyd1, 3, Gerdy ten Dam2
& Tarik Möröy1, 31
Institut für Zellbiologie (Tumorforschung), Universitätsklinikum Essen, Virchowstrasse 173, D-45122 Essen, Germany. 2
Nijmegen Center for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands. 3
Present address: Institut de Recherches Cliniques de Montréal, Montréal, Québec H2W 1R7, Canada (F.H. and T.M.).
Correspondence should be addressed to Tarik Möröy Tarik.Moroy@ircm.qc.ca By alternative splicing, different isoforms of the transmembrane tyrosine phosphatase CD45 are generated that either enhance or limit T cell receptor signaling. We report here that CD45 alternative splicing is regulated by cooperative action of the splice factor U2AF26 and the transcription factor Gfi1. U2AF26 promoted formation of the less-active CD45RO by facilitating exon exclusion. Gfi1 antagonized that process by directly interacting with U2AF26, identifying a previously unknown link between a transcription factor and alternative splicing. The presence of Gfi1 led to formation of the more-active CD45RB, whereas loss of Gfi1 favored CD45RO production. We propose that the relative abundance of U2AF26 and Gfi1 determines the ratio of CD45 isoforms, thereby regulating T cell activation.
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