Abstract:
:Signal-induced alternative splicing of the CD45 gene in human T cells is essential for proper immune function. Skipping of the CD45 variable exons is controlled, in large part, by the recruitment of PSF to the pre-mRNA substrate upon T cell activation; however, the signaling cascade leading to exon exclusion has remained elusive. Here we demonstrate that in resting T cells PSF is directly phosphorylated by GSK3, thus promoting interaction of PSF with TRAP150, which prevents PSF from binding CD45 pre-mRNA. Upon T cell activation, reduced GSK3 activity leads to reduced PSF phosphorylation, releasing PSF from TRAP150 and allowing it to bind CD45 splicing regulatory elements and repress exon inclusion. Our data place two players, GSK3 and TRAP150, in the complex network that regulates CD45 alternative splicing and demonstrate a paradigm for signal transduction from the cell surface to the RNA processing machinery through the multifunctional protein PSF.
journal_name
Mol Celljournal_title
Molecular cellauthors
Heyd F,Lynch KWdoi
10.1016/j.molcel.2010.09.013subject
Has Abstractpub_date
2010-10-08 00:00:00pages
126-37issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(10)00715-Xjournal_volume
40pub_type
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