IRES-mediated translation during cellular stress

细胞应激期间 IRES 介导的翻译

• 批准号: 311935-2011
• 负责人: Hirasawa, Kensuke(Ken)
• 金额: $ 2.19万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526317
• 关键词: IRES; mediated; translation; during; cellular

Cells have two distinct ways to generate proteins which are cap-dependent translation and internal ribosomal entry site (IRES) mediated translation. The majority of cellular proteins are generated via cap-dependent translation while approximately 5% of cellular mRNA and certain viral mRNA are translated by IRES-mediated translation. We still do not have a clear answer as to why mammalian cells have two distinct translation systems. It is known that IRES-mediated translation is often active or maintained when cap-dependent translation is severely impaired under cellular stress and virus infection. Therefore, it is assumed that it is a fail-safe strategy in which IRES-mediated translation maintains cellular homeostasis as a backup of cap-dependent translation under stress conditions. For viruses, the translational machinery driven by IRES elements may be a great advantage for their replication since efficient synthesis of viral proteins can be achieved during cell death. The long-term research goal of our laboratory is to study how cells regulate the two translational machineries in different cellular environment. During the current NSERC funding period (2006-2011), we found that amino acid starvation increase translation efficiency initiated by foot-and-mouth disease virus (FMDV) IRES element. In the proposed study, we will investigate cellular mechanisms of how protein synthesis by FMDV is increased during amino acid starvation. The proposed study will have a significant impact in the field of translational control, virology and cell physiology. In order to understand how protein synthesis is regulated, it is essential that we continue to investigate the mechanisms that underlie IRES-mediated translation and to train the next generation of researchers.

细胞有两种不同的方式产生蛋白质，即帽依赖性翻译和内部核糖体进入位点（IRES）介导的翻译。大多数细胞蛋白是通过帽子依赖性翻译产生的，而大约 5% 的细胞 mRNA 和某些病毒 mRNA 是通过 IRES 介导的翻译来翻译的。关于为什么哺乳动物细胞有两种不同的翻译系统，我们仍然没有明确的答案。众所周知，当帽依赖性翻译在细胞应激和病毒感染下严重受损时，IRES 介导的翻译通常是活跃的或维持的。因此，假设这是一种自动防故障策略，其中 IRES 介导的翻译维持细胞稳态，作为应激条件下帽依赖性翻译的备份。对于病毒来说，IRES元件驱动的翻译机制可能对其复制有很大的优势，因为在细胞死亡过程中可以实现病毒蛋白的有效合成。我们实验室的长期研究目标是研究细胞在不同的细胞环境中如何调节这两种翻译机制。在目前的NSERC资助期间（2006-2011），我们发现口蹄疫病毒（FMDV）IRES元件引发的氨基酸饥饿提高了翻译效率。在拟议的研究中，我们将研究口蹄疫病毒在氨基酸饥饿期间如何增加蛋白质合成的细胞机制。拟议的研究将对翻译控制、病毒学和细胞生理学领域产生重大影响。为了了解蛋白质合成是如何调节的，我们有必要继续研究 IRES 介导的翻译机制并培训下一代研究人员。