Ny T, Elgh F, Lund B
Proc Natl Acad Sci U S A. 1984 Sep;81(17):5355-9. doi: 10.1073/pnas.81.17.5355.
A genomic clone carrying the human tissue-type plasminogen activator (t-PA) gene was isolated from a cosmid library, and the gene structure was elucidated by restriction mapping, Southern blotting, and DNA sequencing. The cosmid contained all the coding parts of the mRNA, except for the first 58 bases in the 5' end of the mRNA, and had a total length of greater than 20 kilobases. It was separated into at least 14 exons by at least 13 introns, and the exons seemed to code for structural or functional domains. Thus, the signal peptide, the propeptide, and the domains of the heavy chain, including the regions homologous to growth factors, and to the "finger" structure of fibronectin, are all encoded by separate exons. In addition, the two kringle regions of t-PA were both coded for by two exons and were cleaved by introns at identical positions. The region coding for the light chain, comprising the serine protease part of the molecule was split by four introns, revealing a gene organization similar to other serine proteases.
从黏粒文库中分离出一个携带人组织型纤溶酶原激活剂（t-PA）基因的基因组克隆，并通过限制性酶切图谱分析、Southern印迹法和DNA测序阐明了该基因的结构。该黏粒包含mRNA的所有编码部分，但不包括mRNA 5'端的前58个碱基，全长超过20千碱基。它被至少13个内含子分隔成至少14个外显子，外显子似乎编码结构域或功能域。因此，信号肽、前肽以及重链的结构域，包括与生长因子和纤连蛋白“指”结构同源的区域，均由不同的外显子编码。此外，t-PA的两个kringle区域均由两个外显子编码，并在相同位置被内含子切割。编码轻链的区域，即分子的丝氨酸蛋白酶部分，被四个内含子分隔，显示出与其他丝氨酸蛋白酶相似的基因组织。
