Paes de Faria Joana, Fernandes Lisete
Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6 Apartado 14, 2780-156 Oeiras, Portugal.
Free Radic Biol Med. 2006 Dec 1;41(11):1684-93. doi: 10.1016/j.freeradbiomed.2006.09.003. Epub 2006 Sep 8.
The general transcription factor TFIIB, encoded by SUA7 in Saccharomyces cerevisiae, is required for transcription activation but apparently of a specific subset of genes, for example, linked with mitochondrial activity and hence with oxidative environments. Therefore, studying SUA7/TFIIB as a potential target of oxidative stress is fundamental. We found that controlled SUA7 expression under oxidative conditions occurs at transcriptional and mRNA stability levels. Both regulatory events are associated with the transcription activator Yap1 in distinct ways: Yap1 affects SUA7 transcription up regulation in exponentially growing cells facing oxidative signals; the absence of this activator per se contributes to increase SUA7 mRNA stability. However, unlike SUA7 mRNA, TFIIB abundance is not altered on oxidative signals. The biological impact of this preferential regulation of SUA7 mRNA pool is revealed by the partial suppression of cellular oxidative sensitivity by SUA7 overexpression, and supported by the insights on the existence of a novel RNA-binding factor, acting as an oxidative sensor, which regulates mRNA stability. Taken together the results point out a primarily cellular commitment to guarantee SUA7 mRNA levels under oxidative environments.
通用转录因子TFIIB由酿酒酵母中的SUA7编码,它是转录激活所必需的,但显然只是特定基因子集所必需的,例如,与线粒体活性相关从而与氧化环境相关的基因。因此,将SUA7/TFIIB作为氧化应激的潜在靶点进行研究至关重要。我们发现,在氧化条件下,SUA7的表达调控发生在转录水平和mRNA稳定性水平。这两个调控事件都以不同方式与转录激活因子Yap1相关:Yap1在面临氧化信号的指数生长细胞中影响SUA7转录上调;该激活因子的缺失本身会导致SUA7 mRNA稳定性增加。然而,与SUA7 mRNA不同,TFIIB的丰度在氧化信号作用下不会改变。SUA7 mRNA库的这种优先调控的生物学影响通过SUA7过表达对细胞氧化敏感性的部分抑制得以揭示,并得到了关于一种新型RNA结合因子存在的见解的支持,该因子作为氧化传感器调节mRNA稳定性。综合这些结果表明,细胞主要致力于在氧化环境下保证SUA7 mRNA水平。