Acute exercise modulates the skeletal muscle nuclear proteome

Exercise is firmly established as a key contributor to overall health stemming from transcriptional remodeling, underpinning its beneficial adaptations. While extensive research has been devoted to understanding the transcriptional response to exercise, our knowledge of the protein constituents of nuclear processes that accompany transcription in skeletal muscle remain less understood. We hypothesize that alterations in the nuclear proteome following exercise hold vital clues for comprehending the transcriptional response and other related nuclear processes. Consequently, we isolated skeletal muscle nuclei from C57BL/6 mice immediately post-, 1-hour, and 4-hours after a 30-minute treadmill running session, to gain insights into the nuclear proteome after exercise. We first detail the successful isolation of skeletal muscle nuclei and the capture of proteins linked to nuclear processes. Of the 2,030 proteins identified, a substantial number encompassed a diverse range of functions including transcription, RNA processing, histone and chromatin modifications, as well as nucleocytoplasmic transport not routinely found in traditional whole skeletal muscle proteomic approaches. Importantly, we found prominent changes in proteins affected by exercise linked to mRNA processing and splicing. In summary, these findings show the importance of improving resolution of nuclear proteins in skeletal muscle and provide evidence of exercise-induced modulations within the skeletal muscle nuclear proteome, offering valuable insights into the broader landscape of the impact from acute exercise. This study is supported by NIH grants U01AG055137. In addition, this study is also supported by U01HL148860 (to JNA, GCC). 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.