Department of Cell Biology and Genetics, Erasmus MC, University medical center Rotterdam, Rotterdam, The Netherlands.
Cell Cycle. 2009 Nov 1;8(21):3462-8. doi: 10.4161/cc.8.21.9835. Epub 2009 Nov 17.
DNA damage induced by UV irradiation provokes profound changes in gene expression. Both transcriptional regulation and posttranslational modification of proteins have been known for many years, but the involvement of microRNAs in regulation of mRNA translation has been described only recently. This level of gene expression regulation appears to operate at the intermediate time points between fast protein modifications (within minutes) and much slower transcriptional reprogramming (which takes several hours to days to develop). MicroRNAs most clearly contribute to regulation of cell cycle checkpoints and apoptosis, but may also influence other aspects of cellular metabolism, differentiation and proliferation. Interestingly, the RNA silencing machinery redistributes into cytoplasmic RNA granules, termed stress granules (SGs), in cells that go through mitosis after UV irradiation. We discuss the implications of these findings for our understanding of the DNA damage response.
紫外线照射引起的 DNA 损伤会引发基因表达的深刻变化。多年来,人们已经知道转录调控和蛋白质的翻译后修饰,但最近才描述了 microRNAs 在调节 mRNA 翻译中的作用。这种基因表达调控水平似乎在快速蛋白质修饰(数分钟内)和慢得多的转录重编程(数小时至数天发展)之间的中间时间点发挥作用。microRNAs 最明显地参与细胞周期检查点和细胞凋亡的调控,但也可能影响细胞代谢、分化和增殖的其他方面。有趣的是,在紫外线照射后经历有丝分裂的细胞中,RNA 沉默机制重新分布到细胞质 RNA 颗粒中,称为应激颗粒 (SGs)。我们讨论了这些发现对我们理解 DNA 损伤反应的意义。