Changes in ribosome content and ribosomal protein expression in denervated mouse skeletal muscle

Skeletal muscle mass is regulated by the balance of protein synthesis and breakdown. Protein synthesis is upregulated during denervation-induced muscle atrophy, although the net balance of protein metabolism turns to negative due to increased protein breakdown. However, changes in ribosome content and ribosomal protein expression after muscle denervation are not clear. In the present study, we aimed to examine whether changes in ribosome content and ribosomal protein expression are involved in the activation of protein synthesis after muscle denervation. Six-month-old male C57BL/6J mice were subjected to unilateral sciatic nerve transection surgery and the contralateral hindlimb served as a sham-operated control. After 2 weeks of surgery, gastrocnemius muscle and extensor digitorum longus muscle was collected. Denervation reduced gastrocnemius muscle mass, but increased phosphorylation of ribosomal protein S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), downstream targets of mechanistic target of rapamycin complex 1 (mTORC1), and ribosomal protein S6 (Rps6) phosphorylation. Consistent with denervation-induced mTORC1 activation, protein synthesis was also increased by denervation. After denervation, total RNA content and 18S and 28S ribosomal RNA (rRNA) per muscle mass increased. Denervation also increased mRNA levels of ribosomal protein-coding genes, Rpl3, Rps6, and Rps18. On the other hand, mRNA levels of Rpl3l, which is a paralogue of Rpl3 and muscle-specific ribosomal protein, was decreased after denervation. Furthermore, we found positive relationship between the level of Rpl3 expression and protein synthesis in individual myofiber of sham and denervated muscle. These observations indicate that while ribosome content per muscle mass increases after denervation, changes in ribosomal composition might not be uniform. This study was partly supported by JST SPRING, Grant Number JPMJSP2108. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.