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

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^*

来源：Nature Communications, 2013, 4(1): 2388.

DOI：10.1038/ncomms3388

Upon muscle injury, the high mobility group box 1 (HMGB1) protein is upregulated 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, HuR binding sites (HuRBS), located in the 3%26apos;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.

• 出版日期2013-9