Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w
Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w
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miR-184 的氧化修饰使其能够靶向 Bcl-xL 和 Bcl-w
DOI：
10.1016/j.molcel.2015.05.003
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发表时间：
2015-07-02
期刊：
影响因子：
16
通讯作者：
Li, Pei-Feng
中科院分区：
文献类型：
--
作者：
Wang, Jian-Xun;Gao, Jie;Li, Pei-Feng
微小RNA（miRNAs）是小的非编码RNA，它们与靶mRNA转录物的三个主要非翻译区（30个UTR）中的互补序列结合，从而抑制mRNA翻译或促进mRNA降解。过量的活性氧（ROS）可通过氧化修饰大分子导致其不适当的功能而引起细胞损伤作用。这种氧化修饰与癌症、衰老、神经退行性疾病和心血管疾病有关。在这里，我们报告说，miRNA可以被ROS氧化修饰。我们发现，miR-184在氧化修饰后与Bcl-xL和Bcl-w的30个UTR结合，这些UTR不是其天然靶点。在大鼠心脏细胞系H9 c2和小鼠模型的研究中，氧化的miR-184与Bcl-xL和Bcl-w的错配参与了细胞凋亡的启动。我们的研究结果揭示了ROS通过氧化修饰miRNA调节细胞事件的模型。
MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (30 UTRs) of target mRNA transcripts, thereby inhibiting mRNA translation or promoting mRNA degradation. Excessive reactive oxygen species (ROS) can cause cell-damaging effects through oxidative modification of macromolecules leading to their inappropriate functions. Such oxidative modification is related to cancers, aging, and neurodegenerative and cardiovascular diseases. Here we report that miRNAs can be oxidatively modified by ROS. We identified that miR-184 upon oxidative modification associates with the 30 UTRs of Bcl-xL and Bcl-w that are not its native targets. The mismatch of oxidized miR-184 with Bcl-xL and Bcl-w is involved in the initiation of apoptosis in the study with rat heart cell line H9c2 and mouse models. Our results reveal a model of ROS in regulating cellular events by oxidatively modifying miRNA.