Tröster H, Metzger T E, Semsei I, Schwemmle M, Winterpacht A, Zabel B, Bachmann M
Institute für Physiologische Chemie, Johannes-Gutenberg Universität, Mainz, Germany.
J Exp Med. 1994 Dec 1;180(6):2059-67. doi: 10.1084/jem.180.6.2059.
A cDNA library was prepared from peripheral blood lymphocytes of an autoimmune patient with primary Sjögrens' syndrome. The cDNA library was screened with the patients own autoimmune serum being monospecific for the nuclear autoantigen La/SS-B. Thereby an alternative type of La mRNA was identified that differed from the known La mRNA due to an exchange of the exon 1. Sequencing of the genomic region between the exons 1 and 2 showed that the alternative 5'-end is a part of the intron. In addition, the presence of an alternative promoter site, which exists within the intron downstream of the exon 1, became evident. In consequence, the alternative La mRNA is the result of a promoter switching combined with an alternative splicing mechanism. In the intron, further transcription factor binding sites, including a NF-kappa B element, were identified leading to the suggestion that the expression of the gene encoding for the nuclear autoantigen La/SS-B alters in dependence on disease conditions.
从一名患有原发性干燥综合征的自身免疫患者的外周血淋巴细胞中制备了一个cDNA文库。用该患者自身对核自身抗原La/SS-B具有单特异性的自身免疫血清筛选该cDNA文库。由此鉴定出一种替代类型的La mRNA，由于外显子1的交换，它与已知的La mRNA不同。外显子1和2之间基因组区域的测序表明，替代的5'-末端是内含子的一部分。此外，外显子1下游内含子内存在替代启动子位点变得明显。因此，替代的La mRNA是启动子切换与替代剪接机制相结合的结果。在内含子中，鉴定出了包括NF-κB元件在内的更多转录因子结合位点，这表明编码核自身抗原La/SS-B的基因的表达根据疾病状况而改变。
