Martin Ryan A, Viggars Mark R, Sanford James A, Taylor Zane W, Hansen Joshua R, Clair Geremy C, Adkins Joshua N, Douglas Collin M, Esser Karyn A
Department of Physiology and Aging, University of Florida, Gainesville, FL, USA.
Myology Institute, University of Florida, Gainesville, FL, USA.
bioRxiv. 2024 Aug 9:2024.08.08.607176. doi: 10.1101/2024.08.08.607176.
Exercise is firmly established as a key contributor to overall well-being and is frequently employed as a therapeutic approach to mitigate various health conditions. One pivotal aspect of the impact of exercise lies in the systemic transcriptional response, which underpins 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 gene expression in skeletal muscle remains largely elusive. We hypothesize that alterations in the nuclear proteome following exercise hold vital clues for comprehending the transcriptional regulation and other related nuclear functions. We isolated skeletal muscle nuclei from C57BL/6 mice both sedentary control and one-hour post 30-minute treadmill running, to gain insights into the nuclear proteome after exercise. A substantial number of the 2,323 proteins identified, were related to nuclear functions. For instance, we found 59 proteins linked to nucleocytoplasmic transport were higher in sedentary mice compared to exercise, hinting at an exercise-induced modulation to nuclear trafficking. Furthermore, 135 proteins exhibited increased abundance after exercise (FDR < 0.1) while 89 proteins decreased, with the most prominent changes in proteins linked to mRNA processing and splicing. Super resolution microscopy further highlights potential localization change in mRNA processing proteins post-exercise, further suggesting changes in nuclear transport dynamics. Nonetheless, our data provide important considerations for the study of the nuclear proteome and supports a paradigm through which exercise downregulated mRNA processing and splicing, offering valuable insights into the broader landscape of the impact from acute exercise.
NEW & NOTEWORTHY: Exercise plays a crucial role in promoting muscle health, but our understanding of nuclear proteins orchestrating exercise responses is limited. Isolation of skeletal muscle nuclei coupled with mass spectrometry enhanced the identification of nuclear proteins. This approach was used to investigate the effects of acute exercise, revealing changes in the muscle nuclear proteome 1-hour post-exercise, including proteins linked to post-transcriptional processing and splicing. Our findings offer insights into the exercise-induced changes within muscle nuclear proteins.
运动已被确认为整体健康的关键因素，并经常被用作缓解各种健康状况的治疗方法。运动影响的一个关键方面在于全身转录反应，这是其有益适应性的基础。虽然已经进行了广泛的研究来理解运动的转录反应，但我们对骨骼肌中伴随基因表达的核过程的蛋白质成分仍然知之甚少。我们假设运动后核蛋白质组的变化为理解转录调控和其他相关核功能提供了重要线索。我们从久坐不动的C57BL/6小鼠以及30分钟跑步机跑步后1小时的小鼠中分离出骨骼肌细胞核，以深入了解运动后的核蛋白质组。在鉴定出的2323种蛋白质中，有相当一部分与核功能有关。例如，我们发现与核质运输相关的59种蛋白质在久坐小鼠中比运动小鼠中含量更高，这表明运动诱导了核运输的调节。此外，135种蛋白质在运动后丰度增加（错误发现率<0.1），而89种蛋白质减少，与mRNA加工和剪接相关的蛋白质变化最为显著。超分辨率显微镜进一步突出了运动后mRNA加工蛋白潜在的定位变化，进一步表明核运输动力学的变化。尽管如此，我们的数据为核蛋白质组的研究提供了重要的思考，并支持了一种运动下调mRNA加工和剪接的模式，为急性运动影响的更广泛图景提供了有价值的见解。
运动在促进肌肉健康方面起着至关重要的作用，但我们对协调运动反应的核蛋白的了解有限。骨骼肌细胞核的分离与质谱联用增强了核蛋白的鉴定。这种方法被用于研究急性运动的影响，揭示了运动后1小时肌肉核蛋白质组的变化，包括与转录后加工和剪接相关的蛋白质。我们的发现为运动诱导的肌肉核蛋白变化提供了见解。
