Liu C Y, Zhu G, Converse R, Kao C W, Nakamura H, Tseng S C, Mui M M, Seyer J, Justice M J, Stech M E
Department of Ophthalmology, University of Cincinnati, Ohio 45267-0527.
J Biol Chem. 1994 Oct 7;269(40):24627-36.
Keratins are a group of water-insoluble proteins constituting paired acidic and basic keratin molecules that form 10-nm intermediate filaments in epithelial cells. Expression of the K3/K12 keratin pair characterizes the cornea-type differentiation. However, the mechanism that regulates this cornea-specific K12 expression remains unknown. To provide a better understanding of the cornea-specific expression, we have cloned the K12 cDNA (Liu, C.-Y., Zhu, G., Westerhausen-Larson, A., Converse, R., Kao, C. W.-C., Sun, T.-T., and Kao, W. W.-Y. (1993) Curr. Eye Res. 12, 963-974). In present studies, the murine K12 keratin gene (Krt1.12) was isolated and characterized. The murine Krt1.12 gene spans 6,567 base pairs of genomic DNA, and the mRNA encoding K12 keratin is distributed into eight exons. Chromosome mapping reveals that murine Krt1.12 is located within the Krt1 complex of mouse chromosome 11. In addition to the production of authentic K12 mRNA, the Krt1.12 gene gives rise to several alternate poly(A)+ RNAs by the use of alternative splicing in intron 2, an alternative promoter in intron 1, and/or both. Sequence analysis indicates that the transcripts derived from alternative splicing and/or the alternative promoter do not have a long open reading frame for keratin or keratin-like molecules. It is not known whether these alternate K12 poly(A)+ RNAs have any biological functions, e.g. regulation of K12 gene expression.
角蛋白是一组水不溶性蛋白质，由成对的酸性和碱性角蛋白分子组成，这些分子在上皮细胞中形成10纳米的中间丝。K3/K12角蛋白对的表达是角膜型分化的特征。然而，调节这种角膜特异性K12表达的机制仍然未知。为了更好地理解角膜特异性表达，我们克隆了K12 cDNA（刘，C.-Y.，朱，G.，韦斯特豪森-拉尔森，A.，康弗斯，R.，考，C. W.-C.，孙，T.-T.，和考，W. W.-Y.（1993年）《当前眼科研究》12卷，963 - 974页）。在目前的研究中，分离并鉴定了小鼠K12角蛋白基因（Krt1.12）。小鼠Krt1.12基因跨越6567个碱基对的基因组DNA，编码K12角蛋白的mRNA分布在8个外显子中。染色体定位显示，小鼠Krt1.12位于小鼠11号染色体的Krt1复合体中。除了产生真实的K12 mRNA外，Krt1.12基因还通过使用内含子2中的可变剪接、内含子1中的可变启动子和/或两者，产生几种可变的聚腺苷酸加尾RNA。序列分析表明，来自可变剪接和/或可变启动子的转录本没有角蛋白或角蛋白样分子的长开放阅读框。尚不清楚这些可变的K12聚腺苷酸加尾RNA是否具有任何生物学功能，例如K12基因表达的调节。
