A Novel Method for Visualizing In-Vivo Rates of Protein Degradation Provides Insight into how TRIM28 Regulates Muscle Size

Skeletal muscle size is controlled by the balance between protein synthesis and protein degradation. Given the essential role of skeletal muscle in maintaining a high quality of life, understanding the mechanisms that modulate this balance are of critical importance. Previously, we demonstrated that muscle-specific knockout of TRIM28 reduces muscle size and function, and in the current study, we discovered that this effect is associated with an increase in protein degradation and a dramatic reduction in the expression of Mettl21c. Importantly, we also determined that overexpression of Mettl21c is sufficient to induce hypertrophy in both control TRIM28 knockout muscles. Moreover, we developed a simple pulse-chase biorthogonal non-canonical amino acid tagging technique that enabled us to visualize the in-vivo rate of protein degradation, and with this technique were able to conclude that the hypertrophic effect of Mettl21c is due, at least in part, to an inhibition of protein degradation. RNA-seq of mouse plantaris muscles. Four replicates each of: Wild Type Sham TRIM28 mKO Sham Wild Type MTE TRIM28 mKO MTE