ANALYSIS OF OXIDATIVE STRESS PROTEINS IN S POMBE

粟酒裂殖酵母中氧化应激蛋白的分析

• 批准号: 7420714
• 负责人: PAUL RUSSELL
• 金额: $ 0.29万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7420714
• 关键词: RNA binding protein; gene expression; oxidative stress; proteins; role; stress

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Eukaryotic cells reprogram their global patterns of gene expression in response to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA-binding protein Csx1 plays a central role in controlling gene expression during oxidative stress. It does so by stabilizing atf1(+) mRNA, which encodes a subunit of a bZIP transcription factor required for gene expression during oxidative stress. Here, we describe two related proteins, Cip1 and Cip2, that were identified by multidimensional protein identification technology (MudPIT) as proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins that have RNA recognition motifs (RRMs). Neither protein is essential for viability, but a cip1Delta cip2Delta strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert posttranscriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1Delta cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1Delta and cip2Delta mutations. This study emphasizes the importance of a modulated mRNA stability in the eukaryotic stress response pathways and adds new information to the role of RNA-binding proteins in the oxidative stress response.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。真核细胞重新编程其基因表达的整体模式以应对压力。最近对粟酒裂殖酵母的研究表明，RNA 结合蛋白 Csx1 在氧化应激过程中控制基因表达方面发挥着核心作用。它通过稳定 atf1(+) mRNA 来实现这一点，atf1(+) mRNA 编码氧化应激期间基因表达所需的 bZIP 转录因子的亚基。在这里，我们描述了两种相关蛋白 Cip1 和 Cip2，它们通过多维蛋白鉴定技术 (MudPIT) 鉴定为与 Csx1 共沉淀的蛋白。 Cip1 和 Cip2 是具有 RNA 识别基序 (RRM) 的细胞质蛋白。这两种蛋白质对于生存能力都不是必需的，但 cip1Delta cip2Delta 菌株生长不良并且改变了细胞形态。遗传上位性研究和全基因组表达谱表明，Cip1 和 Cip2 以被 Csx1 抵消的方式发挥基因表达的转录后控制作用。值得注意的是，csx1Delta 细胞对氧化应激的敏感性以及它们无法诱导 Atf1 依赖性基因表达的能力通过 cip1Delta 和 cip2Delta 突变得到部分恢复。这项研究强调了真核应激反应途径中 mRNA 稳定性调节的重要性，并为 RNA 结合蛋白在氧化应激反应中的作用提供了新的信息。