Belanova Anna A, Smirnov Dmitry S, Makarenko Maxim S, Belousova Mariya M, Mashkina Elena V, Aleksandrova Anzhela A, Soldatov Alexander V, Zolotukhin Peter V
Evolution Corporate Group, Cell Physiology Laboratory, Southern Federal University, Rostov-on-Don, Russia.
Academy of Biology and Biotechnology, Southern Federal University, Rostov-on-Don, Russia.
Genet Mol Biol. 2017 Apr-Jun;40(2):515-524. doi: 10.1590/1678-4685-GMB-2016-0005. Epub 2017 May 29.
Pathway activity assessment-based approaches are becoming highly influential in various fields of biology and medicine. However, these approaches mostly rely on analysis of mRNA expression, and total mRNA from a given locus is measured in the majority of cases. Notably, a significant portion of protein-coding genes produces more than one transcript. This biological fact is responsible for significant noise when changes in total mRNA transcription of a single gene are analyzed. The NFE2L2/AP-1 pathway is an attractive target for biomedical applications. To date, there is a lack of data regarding the agreement in expression of even classical target genes of this pathway. In the present paper we analyzed whether transcript variants of GPX2, NQO1 and SQSTM1 were characterized by individual features of expression when HeLa cells were exposed to pro-oxidative stimulation with hydrogen peroxide. We found that all the transcripts (10 in total) appeared to be significantly individually regulated under the conditions tested. We conclude that individual transcripts, rather than total mRNA, are best markers of pathway activation. We also discuss here some biological roles of individual transcript regulation.
基于通路活性评估的方法在生物学和医学的各个领域正变得极具影响力。然而,这些方法大多依赖于对mRNA表达的分析,并且在大多数情况下测量的是来自给定基因座的总mRNA。值得注意的是,相当一部分蛋白质编码基因会产生不止一种转录本。当分析单个基因的总mRNA转录变化时,这一生物学事实会导致显著的噪声。NFE2L2/AP-1通路是生物医学应用的一个有吸引力的靶点。迄今为止,关于该通路甚至经典靶基因表达一致性的数据都很缺乏。在本文中,我们分析了在HeLa细胞受到过氧化氢的促氧化刺激时,GPX2、NQO1和SQSTM1的转录变体是否具有各自独特的表达特征。我们发现,在测试条件下,所有转录本(总共10种)似乎都受到显著的单独调控。我们得出结论,单个转录本而非总mRNA是通路激活的最佳标志物。我们在此还讨论了单个转录本调控的一些生物学作用。