Résumé
Abstract only Several transcriptional mechanisms are known to be involved in the atrophic response of skeletal muscle. However, emerging data lead us to hypothesize that post‐transcriptional events, operating at the level of mRNA stability, are also contributing. We thus initiated a series of studies to determine the role of post‐transcriptional mechanisms in the response of muscle to disuse. Given the key role of AU‐rich elements (ARE) located in the 3′UTR of multiple mRNAs in controlling their stability, we focused on the contribution of RNA‐binding proteins (RBP) known to interact with this cis‐element. Specifically, we examined expression of HuR, AUF1, TTP, BRF1 and KSRP in slow vs fast muscles as well as in denervated muscles. In general, expression of these RBP was higher in slow muscles. Additionally, a time course of hindlimb denervation ranging from 12 hours to 14 days revealed that the major changes occurred early, i.e. within 2 days of denervation. The most dramatic changes consisted in a substantial increase in expression of the mRNA destabilizing factors TTP and its homolog BRF1 in fast muscles. Since these factors bind to ARE found in multiple important mRNAs, our results identify new molecular mechanisms that likely play a key role in the atrophic response of muscle. Also, they provide additional targets that may be useful for developing novel therapeutics aimed at countering muscle atrophy. Funded by CNES, AFM, MDA and CIHR.