Steinert Nathaniel D, Jorgenson Kent W, Lin Kuan-Hung, Hermanson Jake B, Lemens Jake L, Hornberger Troy A
Department of Comparative Biosciences, University of Wisconsin - Madison, Madison, WI, USA.
School of Veterinary Medicine, University of Wisconsin - Madison, Madison, WI, USA.
iScience. 2023 Mar 30;26(4):106526. doi: 10.1016/j.isci.2023.106526. eCollection 2023 Apr 21.
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 and TRIM28 knockout muscles. Moreover, we developed a simple pulse-chase biorthogonal non-canonical amino acid tagging technique that enabled us to visualize the 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.
骨骼肌的大小由蛋白质合成与蛋白质降解之间的平衡所控制。鉴于骨骼肌在维持高质量生活方面的重要作用，了解调节这种平衡的机制至关重要。此前，我们证明了TRIM28在肌肉中的特异性敲除会减小肌肉大小并降低肌肉功能，在当前研究中，我们发现这种效应与蛋白质降解增加以及Mettl21c表达的显著降低有关。重要的是，我们还确定Mettl21c的过表达足以在对照肌肉和TRIM28敲除肌肉中诱导肥大。此外，我们开发了一种简单的脉冲追踪生物正交非天然氨基酸标记技术，使我们能够可视化蛋白质降解速率，并且通过该技术能够得出结论，Mettl21c的肥大效应至少部分归因于对蛋白质降解的抑制。
