引言
紫外线(UV)辐射会诱导DNA损伤并激活DNA损伤反应(DDR)途径,从而阻滞细胞周期为DNA修复留出时间,当DNA损伤严重到难以修复时就会激活细胞凋亡【1-3】。UV辐射诱导DNA损伤的研究早已被人们熟知,但是关于UV也可以诱导RNA损伤的产生却较少被提及。有研究发现,UV可以通过光化学反应生成嘧啶二聚体和其他光产物,这些产物可以诱导转录组范围内的RNA损伤,同时UV损伤还会导致翻译缺陷,核糖体会停滞在富含嘧啶的受损密码子上,引起核糖体碰撞,从而激活核糖毒性应激反应(ribotoxic stress response, RSR)【4-5】。RSR将会激活下游的ZAK和GCN2激酶,ZAK激酶激活MAPK途径介导细胞周期停滞和细胞凋亡,GCN2激酶的激活导致eIF2α磷酸化和通过整合应激反应(ISR)介导的蛋白合成抑制【6-10】。虽然已经发现UV诱导的RNA损伤可以通过核糖体碰撞激活RSR和ISR通路,但是这些研究未能解决一个关键问题:细胞如何整合这些反应来决定细胞的命运。
7月11日,来自美国约翰霍普金斯大学医学院的Rachel Green课题组在Cell上发表了研究论文The ribotoxic stress response drives UV-mediated cell death。在本研究中,作者通过全面的分析揭示了UV照射后细胞内发生的各种核酸损伤应激反应作用,发现RSR在UV依赖的程序性细胞死亡中比DDR起到更为关键的作用。这一发现突破了传统的认知,为理解细胞如何应对UV损伤提供了新的见解。

参考文献
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排版|探索君
文章来源|“BioArt”
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