Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w

• DOI: 10.1016/j.molcel.2015.05.003
• Publication Date: 2015-05-29T09:00:54Z
• Authors: Jian-Xun Wang; Jie Gao; Su-Ling Ding; Kun Wang; Jian-Qin Jiao; Yin Wang; Teng Sun; Lu-Yu Zhou; Bo Long; Xiao-Jie Zhang; Qian Li; Jin-Ping Liu; Chang Feng; Jia Liu; Ying Gong; Zhixia Zhou; Pei-Feng Li
• Keywords: Male; 0301 basic medicine; 2. Zero hunger; Myocardium; bcl-X Protein; Proteins; Apoptosis; Cell Biology; Cell Line; Rats; 3. Good health; Mice, Inbred C57BL; Mice; MicroRNAs; 03 medical and health sciences; Animals; RNA Interference; RNA, Small Interfering; Apoptosis Regulatory Proteins; Reactive Oxygen Species; Molecular Biology; 3' Untranslated Regions; Oxidation-Reduction

MicroRNAs (miRNAs) are small non-coding RNAs, and they bind to complementary sequences in the three prime untranslated regions (3' 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 3' 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.