Abstract:
Alternative splicing is a part of mRNA processing that expands the diversity of proteins encoded by a single gene. Studying the full range of proteins-products of translation of alternatively spliced mRNA is extremely important for understanding the interactions between receptor proteins and ligands since different receptor protein isoforms can provide variation in the activation of signaling pathways. In this study, we investigated the expression of isoforms of TNFR1 and TNFR2 receptors before and after exposure to TNFα in two cell lines that had previously demonstrated diverse effects on cell proliferation under TNFα incubation using RT-qPCR. We found that after incubation with TNFα: (1) expression of isoform 3 of the TNFRSF1A gene was increased in both cell lines; (2) the cell line with increased proliferation, K562, had decreased expression of isoforms 1 and 4 of the TNFRSF1A gene and expression of isoform 2 of TNFRSF1B gene was absent at all; (3) the cell line with decreased proliferation-MCF-7 had significantly increased expression of isoform 2 of TNFRSF1B gene. Thus, we can conclude that TNFα exposure to the K562 and MCF-7 cell lines leads to changes in the expression of TNFα receptor isoforms, which, in turn, can appear via diverse proliferative effects.
摘要:
可变剪接是mRNA加工的一部分,可扩展单个基因编码的蛋白质的多样性。研究可变剪接mRNA翻译的全部蛋白质-产物对于理解受体蛋白质与配体之间的相互作用极为重要,因为不同的受体蛋白质同工型可以提供信号通路激活的变化。在这项研究中,我们研究了两种细胞系中暴露于TNFα之前和之后的TNFR1和TNFR2受体亚型的表达,这两种细胞系先前使用RT-qPCR在TNFα孵育下对细胞增殖具有不同的影响。我们发现与TNFα孵育后:(1)两种细胞系中TNFRSF1A基因同工型3的表达均增加;(2)增殖增加的细胞系,K562的TNFRSF1A基因的同工型1和4的表达降低,而TNFRSF1B基因的同工型2的表达根本不存在;(3)增殖减少的细胞系MCF-7的TNFRSF1B基因的同工型2的表达显着增加。因此,我们可以得出结论,TNFα暴露于K562和MCF-7细胞系导致TNFα受体亚型表达的变化,which,反过来,可以通过不同的增殖作用出现。