Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada.
Int J Mol Sci. 2020 Sep 11;21(18):6650. doi: 10.3390/ijms21186650.
Protein synthesis, or mRNA translation, is one of the most energy-consuming functions in cells. Translation of mRNA into proteins is thus highly regulated by and integrated with upstream and downstream signaling pathways, dependent on various transacting proteins and cis-acting elements within the substrate mRNAs. Under conditions of stress, such as exposure to ionizing radiation, regulatory mechanisms reprogram protein synthesis to translate mRNAs encoding proteins that ensure proper cellular responses. Interestingly, beneficial responses to low-dose radiation exposure, known as radiation hormesis, have been described in several models, but the molecular mechanisms behind this phenomenon are largely unknown. In this review, we explore how differences in cellular responses to high- vs. low-dose ionizing radiation are realized through the modulation of molecular pathways with a particular emphasis on the regulation of mRNA translation control.
蛋白质合成,即 mRNA 翻译,是细胞中最耗能的功能之一。因此,mRNA 到蛋白质的翻译受到上游和下游信号通路的高度调控,并与底物 mRNA 内的各种反式作用蛋白和顺式作用元件整合。在应激条件下,如暴露于电离辐射下,调节机制会重新编程蛋白质合成,以翻译编码确保细胞适当反应的蛋白质的 mRNA。有趣的是,在几种模型中描述了对低剂量辐射暴露的有益反应,即辐射兴奋效应,但这种现象背后的分子机制在很大程度上尚不清楚。在这篇综述中,我们探讨了通过调节分子途径来实现细胞对高剂量与低剂量电离辐射的反应差异,特别强调了 mRNA 翻译控制的调节。