Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors.
CD45 is a transmembrane glycoprotein possessing tyrosine phosphatase activity, which is involved in cell signaling. CD45 is expressed on the surface of most leukocytes and can be alternatively spliced by the inclusion or skipping of three variable exons (4, 5, and 6 or A, B, and C) to produce up to eight isoforms. In T cells, the splicing pattern of CD45 isoforms changes after activation; naive cells express high m.w. isoforms of CD45 which predominantly express exon A (CD45RA), whereas activated cells lose expression of exon A to form low m.w. isoforms of CD45 including CD45RO. Little is known about the specific factors controlling the switch in CD45 splicing which occurs on activation. In this study, we examined the influence of the SR family of splicing factors, which, like CD45, are expressed in tissue-specific patterns and have been shown to modulate the alternative splicing of a variety of transcripts. We show that specific SR proteins have antagonistic effects on CD45 splicing, leading either to exon inclusion or skipping. Furthermore, we were able to demonstrate specific changes in the SR protein expression pattern during T cell activation.
ten Dam
G B
GB
Departments of Cell Biology and Anatomy, Faculty of Medical Sciences, University of Nijmegen, Nijmegen, The Netherlands. g.tendam@bioch.kun.nl
Zilch
C F
CF
Wallace
D
D
Wieringa
B
B
Beverley
P C
PC
Poels
L G
LG
Screaton
G R
GR
D017398:Alternative Splicing / Q000276:immunology*; D000818:Animals; D001120:Arginine / Q000502:physiology; D019556:COS Cells; D005091:Exons / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000502:physiology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000502:physiology; D012322:RNA Precursors / Q000502:physiology; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D012694:Serine / Q000502:physiology; D000068103:Serine-Arginine Splicing Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection
D009687:Nuclear Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012322:RNA Precursors; D016601:RNA-Binding Proteins; D000068103:Serine-Arginine Splicing Factors; D012694:Serine; D001120:Arginine; D017493:Leukocyte Common Antigens