c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle
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c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle. / Mori, Takahiro; Ato, Satoru; Knudsen, Jonas Roland; Henriquez-Olguin, Carlos; Li, Zhencheng; Wakabayashi, Koki; Suginohara, Takeshi; Higashida, Kazuhiko; Tamura, Yuki; Nakazato, Koichi; Jensen, Thomas Elbenhardt; Ogasawara, Riki.
In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 321, No. 4, 2021, p. E551-E559.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle
AU - Mori, Takahiro
AU - Ato, Satoru
AU - Knudsen, Jonas Roland
AU - Henriquez-Olguin, Carlos
AU - Li, Zhencheng
AU - Wakabayashi, Koki
AU - Suginohara, Takeshi
AU - Higashida, Kazuhiko
AU - Tamura, Yuki
AU - Nakazato, Koichi
AU - Jensen, Thomas Elbenhardt
AU - Ogasawara, Riki
N1 - CURIS 2021 NEXS 311
PY - 2021
Y1 - 2021
N2 - High-intensity muscle contractions (HiMC) are known to increase c-Myc expression which is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, while c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, this 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 weeks 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-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.
AB - High-intensity muscle contractions (HiMC) are known to increase c-Myc expression which is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, while c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, this 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 weeks 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-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.
KW - Faculty of Science
KW - Exercise
KW - c-Myc
KW - Ribosome biogenesis
KW - Protein matabolism
KW - RNA-Seq
U2 - 10.1152/ajpendo.00164.2021
DO - 10.1152/ajpendo.00164.2021
M3 - Journal article
C2 - 34423683
VL - 321
SP - E551-E559
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 4
ER -
ID: 276706276