c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle
c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle
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DOI：
10.1152/ajpendo.00164.2021
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发表时间：
2021-10-01
影响因子：
5.1
通讯作者：
Ogasawara, Riki
中科院分区：
文献类型：
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作者：
Mori, Takahiro;Ato, Satoru;Ogasawara, Riki
已知高强度肌肉收缩（HiMC）增加c-Myc表达，其已知刺激大多数细胞中的核糖体生物合成和蛋白质合成。然而，虽然c-Myc mRNA转录和c-Myc mRNA翻译已被证明是上调后阻力运动伴随着增加核糖体生物合成，这种连接没有被直接测试。我们研究了腺相关病毒（AAV）介导的c-Myc过表达，有或没有禁食或经皮电刺激诱导的HiMC，对成年小鼠骨骼肌核糖体生物合成和蛋白质合成的影响。AAV介导的c-Myc在小鼠骨骼肌中过表达2周增加了DNA聚合酶亚基POL 1 mRNA、45 S-pre-rRNA、总RNA和肌肉蛋白合成，而不改变随意和禁食条件下雷帕霉素复合物1（mTORC 1）信号传导的机制靶点。RNA-seq分析表明，c-Myc的过表达主要调控核糖体生物发生相关的生物学过程。对c-Myc过表达的蛋白质合成反应反映了HiMC的反应。未观察到c-Myc过表达和HiMC组合的额外作用。我们的研究结果表明，c-Myc的过度表达是足以刺激骨骼肌核糖体的生物合成和蛋白质的合成，而不激活mTORC 1。因此，HiMC诱导的c-Myc增加可能有助于HiMC后核糖体生物合成和蛋白质合成增加。新&值得注意的是，阻力运动已知会增加c-Myc表达，这已知会刺激各种细胞中的核糖体生物合成和蛋白质合成。然而，c-Myc的增加是否刺激骨骼肌中的核糖体生物合成和蛋白质合成仍然未知。我们发现，c-Myc过表达足以刺激骨骼肌核糖体生物合成和蛋白质合成，而不激活mTORC 1。
High-intensity muscle contractions (HiMCs) are known to increase c-Myc expression that is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, although c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, this connection has not been tested directly. We investigated the effect of adeno-associated virus (AAV)-mediated c-Myc overexpression, with or without fasting or percutaneous electrical stimulation-induced HiMC, on ribosome biogenesis and protein synthesis in adult mouse skeletal muscles. AAV-mediated overexpression of c-Myc in mouse skeletal muscles for 2 wk increased the DNA polymerase subunit POL1 mRNA, 45S-pre-rRNA, total RNA, and muscle protein synthesis without altering mechanistic target of rapamycin complex 1 (mTORC1) signaling under both ad libitum and fasted conditions. RNA-sequencing (RNA-seq) analyses revealed that c-Myc overexpression mainly regulated ribosome biogenesis-related biological processes. The protein synthesis response to c-Myc overexpression mirrored the response with HiMC. No additional effect of combining c-Myc overexpression and HiMC was observed. Our results suggest that c-Myc overexpression is sufficient to stimulate skeletal muscle ribosome biogenesis and protein synthesis without activation of mTORC1. Therefore, the HiMC-induced increase in c-Myc may contribute to ribosome biogenesis and increased protein synthesis following HiMC.NEW & NOTEWORTHY Resistance exercise is known to increase c-Myc expression, which is known to stimulate ribosome biogenesis and protein synthesis in a variety of cells. However, whether the increase in c-Myc stimulates ribosome biogenesis and protein synthesis in skeletal muscles remains unknown. We found that c-Myc overexpression is sufficient to stimulate skeletal muscle ribosome biogenesis and protein synthesis without activation of mTORC1.