HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA.

HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA.
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DOI:
10.1038/ncomms3388
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发表时间:
2013
影响因子:
16.6
通讯作者:
Gallouzi, Imed-Eddine
Gallouzi, Imed-Eddine
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Dormoy-Raclet, Virginie;Cammas, Anne;Celona, Barbara;Lian, Xian Jin;van der Giessen, Kate;Zivojnovic, Marija;Brunelli, Silvia;Riuzzi, Francesca;Sorci, Guglielmo;Wilhelm, Brian T.;Di Marco, Sergio;Donato, Rosario;Bianchi, Marco E.;Gallouzi, Imed-Eddine

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在肌肉损伤时,高迁移率族蛋白1(HMGB 1)蛋白被上调并分泌以启动修复反应。在这里,我们表明,HMGB 1控制肌肉发生在体外和体内,在发展和成人肌肉损伤后。肌肉细胞中的HMGB 1表达在翻译水平上受到调节:miRNA miR-1192抑制HMGB 1翻译,RNA结合蛋白HuR促进HMGB 1翻译。HuR与位于HMGB 1转录本3 'UTR的顺式元件HuRBS结合,同时miR-1192被募集到邻近的种子元件。HuR与HuRBS的结合阻止了Argonaute 2(Ago 2)的募集,克服了miR-1192介导的翻译抑制。耗尽HuR减少成肌细胞融合,沉默miR-1192重新建立HuR耗尽细胞的融合潜力。我们认为HuR通过增强HMGB 1的翻译和抑制miR-1192介导的翻译抑制来促进成肌细胞对肌生成的承诺。
Upon muscle injury the high mobility group box 1 (HMGB1) protein is up-regulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo, during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuRBS, located in the 3′UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192.
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