Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, PR China.
RNA Biol. 2012 Oct;9(10):1247-54. doi: 10.4161/rna.21821. Epub 2012 Aug 24.
Alterations in microRNA (miRNA) expression have been observed in cells subjected to exogenous stresses, implying that miRNAs play an important role in cellular stress response; however, the underlying mechanism is still largely unknown. In the present study, we found that miR-3928 was implicated in cellular response to ionizing radiation. After exposed to X-rays, miR-3928 expression increased in 1.5 h and then decreased, meanwhile Dicer, a key component in the miRNA processing machinery, increased gradually. An oscillation was observed in the expression of both mature miR-3928 and Dicer mRNA from 2 h to 3.5 h in irradiated cells. Then, we verified that miR-3928 directly bound to the 3'-untranslated region of Dicer mRNA. Consequently, Dicer expression was suppressed and the maturation of other miRNAs including miR-185, miR-300, and miR-663, was inhibited. Overexpression of miR-3928 induced DNA damage, activated ATR, and phosphorylated Chk1 accompanied by G1 arrest. Taken together, these findings replenished ATR/Chk1 pathway by revealing a novel miRNA regulatory network in response to exogenous stress, in which miR-3928 plays an important role in regulating the expression of Dicer.
miRNA（微小 RNA）表达的改变已在受到外源压力的细胞中观察到，这意味着 miRNA 在细胞应激反应中发挥重要作用；然而，其潜在机制在很大程度上仍然未知。在本研究中，我们发现 miR-3928 参与细胞对电离辐射的反应。X 射线照射后，miR-3928 的表达在 1.5 小时内增加，然后减少，同时，miRNA 加工机制中的关键成分 Dicer 逐渐增加。在照射细胞中，成熟的 miR-3928 和 Dicer mRNA 的表达从 2 小时到 3.5 小时观察到振荡。然后，我们验证了 miR-3928 直接结合到 Dicer mRNA 的 3'-非翻译区。结果，Dicer 的表达受到抑制，其他 miRNA（包括 miR-185、miR-300 和 miR-663）的成熟受到抑制。miR-3928 的过表达诱导 DNA 损伤，激活 ATR，并磷酸化 Chk1，同时伴有 G1 期阻滞。总之，这些发现通过揭示一种新的 miRNA 调控网络来补充 ATR/Chk1 途径，该网络在外源应激反应中发挥重要作用，其中 miR-3928 在调节 Dicer 的表达中起重要作用。
