Mex-3B induces apoptosis by inhibiting miR-92a access to the Bim-3′UTR
Mex-3B induces apoptosis by inhibiting miR-92a access to the Bim-3′UTR
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DOI：
10.1038/s41388-018-0336-7
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发表时间：
2018-09-20
期刊：
影响因子：
8
通讯作者：
Akiyama, Tetsu
中科院分区：
文献类型：
--
作者：
Oda, Takeaki;Yamazumi, Yusuke;Akiyama, Tetsu
细胞通过调控调控细胞周期停滞、DNA修复、衰老和/或凋亡的基因来应对包括DNA损伤在内的各种细胞应激。MicroRNAs(MiRNAs)通过破坏mRNAs的稳定性和抑制翻译，在正常发育和疾病发病机制中发挥重要作用。反过来，miRNA的生物发生、周转和活性可以由特定的RNA结合蛋白调节。在这里，我们发现Mex-3B，一个含有hnRNP K同源(KH)结构域的RNA结合蛋白，通过转录后上调促凋亡的BH3(Bcl-2同源区域3)家族成员Bim来关键地调控DNA应激诱导的细胞凋亡。此外，我们的数据表明，Mex-3B与Bim的3‘-非翻译区(3’UTR)的结合干扰了ArgAerte(AGO)-miR-92a复合体与Bim RNA中存在的miR-92a靶点的相互作用。我们的结果为转录后机制提供了新的见解，转录后机制对细胞应激反应至关重要。
Cells respond to a variety of cellular stresses, including DNA damage, by regulating genes whose expression modulates cell cycle arrest, DNA repair, senescence, and/or apoptosis. MicroRNAs (miRNAs) play essential roles in both normal development and disease pathogenesis by destabilizing mRNAs and inhibiting translation. In turn, miRNA biogenesis, turnover, and activity can be regulated by specific RNA-binding proteins. Here we show that Mex-3B, an hnRNP K homology (KH) domain-containing RNA-binding protein, critically modulates DNA stress-induced apoptosis by posttranscriptionally upregulating the pro-apoptotic BH3 (Bcl-2 homology region 3)-only family member Bim. Furthermore, our data indicate that binding of Mex-3B to the 3'-untranslated region (3'UTR) of Bim interferes with the interaction of an Argonaute (Ago)-miR-92a complex with a miR-92a target site present in the Bim RNA. Our results provide novel insights into the posttranscriptional mechanisms that are critical for cellular stress responses.