γ射线诱导的小鼠5S 核糖体RNA表达水平变化及其机制研究

电离辐射诱导的5S 核糖体RNA表达变化及其变化机制的研究对于深入了解辐射调控蛋白质合成的机制具有重要意义。转录因子ⅢA是5S核糖体RNA表达的转录因子，电离辐射产生的自由基很有可能通过氧化还原作用使转录因子ⅢA的配位锌离子价态发生改变，导致转录因子ⅢA结构和功能变化从而改变5S 核糖体RNA表达水平，但到目前为止转录因子ⅢA作为金属蛋白质所可能特有的金属离子价态变化导致的放射生物效应尚未被关注。本项目围绕γ射线对配位锌离子价态的影响及该影响与TFⅢA功能变化之间关系的关键问题，采用PCR、X射线光电子谱、DNase酶1体外足迹及ChIP等技术，探讨γ射线辐照小鼠淋巴细胞转录因子ⅢA功能变化对5S 核糖体RNA表达水平的影响，为电离辐射调控蛋白质的合成机制研究提供理论依据。本项目首次进行基于金属离子价态变化的金属蛋白质放射生物效应研究，可为放射生物学研究提供新靶点。

The alteration of expression level of 5S ribosomal RNA (5S rRNA) induced by ionizing radiation and its possible mechanism is significant for the field of radiation-regulated protein synthesis. Transcription factor ⅢA (TF ⅢA), a metalloprotein coordinated with zinc ions, is a transcription factor for expression of 5S rRNA. Ionizing radiation generates lots of free radicals which may change the valence state of zinc ions of TF ⅢA through redox reaction. The altered valence state of zinc ions may subsequently cause change of structure and function of TF ⅢA, which has a possibility to change the expression level of 5S rRNA. The main objective of this project is to explore the expression level of 5S rRNA in gamma-irradiated mice and elucidate the change mechanism of 5S rRNA through resolution of key points of how γ-rays induces alteration of the valence state of zinc ions and how the relationship is between alterations of the valence state of zinc ions and function of TF ⅢA. This project firstly performs the study of radiation effects of metalloprotein based on altered valence state of metal ions. The valence state of metal ions coordinated in metalloprotein may be the potential target for study of radiation biological effects.