TY - JOUR
T1 - HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA
AU - Dormoy-Raclet, Virginie
AU - Cammas, Anne
AU - Celona, Barbara
AU - Lian, Xian Jin
AU - Van Der Giessen, Kate
AU - Zivojnovic, Marija
AU - Brunelli, Silvia
AU - Riuzzi, Francesca
AU - Sorci, Guglielmo
AU - Wilhelm, Brian T.
AU - Marco, Sergio Di
AU - Donato, Rosario
AU - Bianchi, Marco E.
AU - Gallouzi, Imed Eddine
PY - 2013
Y1 - 2013
N2 - 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′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.
AB - 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′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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U2 - 10.1038/ncomms3388
DO - 10.1038/ncomms3388
M3 - Article
C2 - 24005720
AN - SCOPUS:84884126014
VL - 4
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2388
ER -