Regulation of alternative splicing of CD45 by antagonistic effects of SR protein splicing factors.
نویسندگان
چکیده
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.
منابع مشابه
Factors Antagonistic Effects of SR Protein Splicing Regulation of Alternative Splicing of CD45 by
متن کامل
Role of Aberrant Alternative Splicing in Cancer
Alternative splicing can alter genome sequence and as a consequence, many genes change to oncogenes. This event can also affect protein function and diversity. The growing number of study elucidate the pathological influence of impaired alternative splicing events on numerous disease including cancer. Here, we would like to highlight the significant role of alternative splicing in cancer biolog...
متن کاملPosition-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms.
Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5' splice sites. SR proteins enhance splicing only when they are recruited to the exon. Ho...
متن کاملRegulated tissue-specific expression of antagonistic pre-mRNA splicing factors.
The SR proteins are essential metazoan pre-mRNA splicing factors that can also influence the selection of alternative 5' splice sites in a concentration-dependent manner. Their activity in alternative splicing in vitro is antagonized by members of the hnRNP A/B family of proteins. The opposite effects of members of these two families of antagonistic splicing factors in vitro and upon overexpres...
متن کاملSodium Butyrate and Valproic Acid as Splicing Restoring Agents in Erythroid Cells of b-Thalassemic Patients
Background: b-Thalassemia is a common autosomal recessive disorder in human caused by a defect in b-globin chain synthesis. The most common mutations causing b-Thalassemia have been found to be splicing mutations. Most of which activate aberrant cryptic splicing/sites without complete disruption of normal splicing. IVSI-110 mutation, a common splicing mutation, leads to a 90% reduction of norma...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 164 10 شماره
صفحات -
تاریخ انتشار 2000