title: Oxidative Modification of miR-184 Enables It to Target Bcl-xL and Bcl-w.
abstract: 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.
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Jian-Xun
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Su-Ling
authors.initials: SL
authors.lastname: Ding
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Jiao
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Sun
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Lu-Yu
authors.initials: LY
authors.lastname: Zhou
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Long
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Feng
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Institute for Translational Medicine, College of Medicine, Qingdao University, Deng Zhou Road 38, Qingdao 266021, China. Electronic address: peifli@qdu.edu.cn.
authors.forename: Pei-Feng
authors.initials: PF
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction; D011506:Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051020:bcl-X Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C494812:Bcl2l1 protein, mouse; C101155:Bcl2l2 protein, mouse; C552233:MIRN184 microRNA, mouse; D035683:MicroRNAs; D011506:Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051020:bcl-X Protein