Liu C, Cheng J, Mountz J D
Department of Medicine, University of Alabama at Birmingham, USA.
Biochem J. 1995 Sep 15;310 ( Pt 3)(Pt 3):957-63. doi: 10.1042/bj3100957.
Human Fas/Apo-1 is a cell-surface protein that mediates apoptosis upon ligation with Fas ligand. The gene lies on the long arm of chromosome 10, consists of nine exons, and spans more than 26 kb of DNA. We previously reported the presence of a Fas variant mRNA, designated as Fas delta TM, in human peripheral blood mononuclear cells. Fas delta TM is generated by alternative splicing of the intact exon 6, which encodes the Fas transmembrane domain. In the present study, we describe three novel forms of Fas mRNA that are generated by alternative splicing of exons 3, 4, 6 and 7. These three mRNA variants undergo a frameshift and produce truncated polypeptides because of the appearance of a stop codon in the altered open reading frame. On activation of the peripheral blood mononuclear cells, a decreased expression of alternatively spliced Fas mRNA species correlated with increased cell-surface expression of Fas. These results suggest that differential expression of alternatively spliced Fas mRNAs may play a role in regulation of Fas function via regulation of the production of the membrane-bound and the soluble, secreted Fas protein products.
人Fas/Apo-1是一种细胞表面蛋白，与Fas配体结合后介导细胞凋亡。该基因位于10号染色体长臂，由9个外显子组成，跨越超过26kb的DNA。我们先前报道在人外周血单个核细胞中存在一种Fas变异mRNA，命名为FasδTM。FasδTM是由完整外显子6的可变剪接产生的，外显子6编码Fas跨膜结构域。在本研究中，我们描述了三种由外显子3、4、6和7的可变剪接产生的新型Fas mRNA形式。由于改变的开放阅读框中出现终止密码子，这三种mRNA变异体发生移码并产生截短的多肽。在外周血单个核细胞激活后，可变剪接的Fas mRNA种类的表达降低与Fas细胞表面表达增加相关。这些结果表明，可变剪接的Fas mRNA的差异表达可能通过调节膜结合型和可溶性分泌型Fas蛋白产物的产生来调节Fas功能。
