scholarly journals RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes

2017 ◽  
Author(s):  
Alexis H Bennett ◽  
Marie-Francoise O’Donohue ◽  
Stacey R. Gundry ◽  
Aye T. Chan ◽  
Jeffery Widrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Translational Control ◽  
Regulation Of Gene Expression ◽  
Muscle Growth ◽  
Rna Helicase ◽  
Genetic Screen ◽  
Control Of Gene Expression ◽  
Muscle Diseases ◽  
Skeletal Muscle Growth

ABSTRACTGene expression in a tissue-specific context depends on the combined efforts of epigenetic, transcriptional and post-transcriptional processes that lead to the production of specific proteins that are important determinants of cellular identity. Ribosomes are a central component of the protein biosynthesis machinery in cells; however, their regulatory roles in the translational control of gene expression in skeletal muscle remain to be defined. In a genetic screen to identify critical regulators of myogenesis, we identified a DEAD-Box RNA helicase, DDX27, that is required for skeletal muscle growth and regeneration. We demonstrate that DDX27 regulates ribosomal RNA (rRNA) maturation, and thereby the ribosome biogenesis and the translation of specific transcripts during myogenesis. These findings provide insight into the translational regulation of gene expression in myogenesis and suggest novel functions for ribosomes in regulating gene expression in skeletal muscles.AUTHOR SUMMARYInherited skeletal muscle diseases are the most common form of genetic disorders with primary abnormalities in the structure and function of skeletal muscle resulting in the impaired locomotion in affected patients. A major hindrance to the development of effective therapies is a lack of understanding of biological processes that promote skeletal muscle growth. By performing a forward genetic screen in zebrafish we have identified mutation in a RNA helicase that leads to perturbations of ribosomal biogenesis pathway and impairs skeletal muscle growth and regeneration. Therefore, our studies have identified novel ribosome-based disease processes that may be therapeutic modulated to restore muscle function in skeletal muscle diseases.

Activation of insulin-like growth factor gene expression during work-induced skeletal muscle growth

1990 ◽  
Vol 259 (1) ◽  
pp. E89-E95 ◽  
Author(s):  
D. L. DeVol ◽  
P. Rotwein ◽  
J. L. Sadow ◽  
J. Novakofski ◽  
P. J. Bechtel
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Growth ◽  
Experimental Period ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Muscle Weight ◽  
Skeletal Muscle Growth ◽  
Igf I

We have investigated the hypothesis that there is local regulation of insulin-like growth factor (IGF) gene expression during skeletal muscle growth. Compensatory hypertrophy was induced in the soleus, a predominantly slow-twitch muscle, and plantaris, a fast-twitch muscle, in 11- to 12-wk-old female Wistar rats by unilateral cutting of the distal gastrocnemius tendon. Animals were killed 2, 4, or 8 days later, and muscles of the nonoperated leg served as controls. Muscle weight increased throughout the experimental period, reaching 127% (soleus) or 122% (plantaris) of control values by day 8. In both growing muscles, IGF-I mRNA, quantitated by a solution-hybridization nuclease-protection assay, rose by nearly threefold on day 2 and remained elevated throughout the experimental period. IGF-II mRNA levels also increased over controls. A more dramatic response was seen in hypophysectomized rats, where IGF-I mRNA levels rose by 8- to 13-fold, IGF-II values by 3- to 7-fold, and muscle mass increased on day 8 to 149% (soleus) or 133% (plantaris) of the control contralateral limb. These results indicate that signals propagated during muscle hypertrophy enhance the expression of both IGF genes, that modulation of IGF-I mRNA levels can occur in the absence of growth hormone, and that locally produced IGF-I and IGF-II may play a role in skeletal muscle growth.

scholarly journals Satellite cell expansion is mediated by P-eIF2α dependent Tacc3 translation

2020 ◽  
Author(s):  
Ryo Fujita ◽  
Graham Lean ◽  
Solène Jamet ◽  
Steven Hébert ◽  
Claudia L. Kleinman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Stem Cell ◽  
Satellite Cells ◽  
Translational Control ◽  
Adult Stem Cell ◽  
Control Of Gene Expression ◽  
Important Regulator ◽  
Stem Cell Populations

AbstractTranslational control of gene expression is an important regulator of adult stem cell quiescence, activation and self-renewal. In skeletal muscle, quiescent satellite cells maintain low levels of protein synthesis, mediated in part through the phosphorylation of eIF2α (P-eIF2α). Pharmacological inhibition of the eIF2α phosphatase with the small molecule sal003 maintains P-eIF2α and permits the expansion of satellite cells ex vivo. Paradoxically, P-eIF2α also increases the translation of specific mRNAs, which is mediated by P-eIF2α dependent readthrough of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2α dependent mRNA translation enables expansion of satellite cells. Using transcriptomic and proteomic analyses, we show a number of genes associated with the assembly of the spindle pole to be upregulated at the level of protein, without corresponding change in mRNA levels, in satellite cells expanded in the presence of sal003. We show that uORFs in the 5’UTR of mRNA for the mitotic spindle stability gene Tacc3 direct P-eIF2α dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle.SignificanceTranslational control of gene expression has emerged as an important regulator of adult stem cell populations, which maintain low levels of protein synthesis. In adult muscle stem cells, or satellite cells, a portrait of translational control has emerged whereby multiple repression mechanisms prevent the translation of specific mRNAs. It remains unclear how other mRNAs escape repression and are efficiently translated. We show that within the context of low global rates of protein synthesis, satellite cell expansion occurs through the selective translation of Tacc3 mRNA. Tacc3 deficient satellite cells expand poorly, leading to defects in skeletal muscle regeneration. Our study provides a more complete picture of translational control of gene expression in adult stem cell populations.

scholarly journals RNA helicase, DDX27 regulates skeletal muscle growth and regeneration by modulation of translational processes

PLoS Genetics ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. e1007226 ◽  
Author(s):  
Alexis H. Bennett ◽  
Marie-Francoise O’Donohue ◽  
Stacey R. Gundry ◽  
Aye T. Chan ◽  
Jeffrey Widrick ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Growth ◽  
Rna Helicase ◽  
Skeletal Muscle Growth

Acute ethanol increases angiogenic growth factor gene expression in rat skeletal muscle

2002 ◽  
Vol 92 (3) ◽  
pp. 1176-1182 ◽  
Author(s):  
Timothy P. Gavin ◽  
Peter D. Wagner
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Acute Exercise ◽  
Muscle Growth ◽  
Angiogenic Growth Factor ◽  
Factor Gene ◽  
Skeletal Muscle Growth ◽  
Growth Factor Gene ◽  
Exercise Induced

Moderate ethanol consumption demonstrates a protective effect against cardiovascular disease and improves insulin sensitivity, possibly through angiogenesis. We investigated whether 1) ethanol would increase skeletal muscle growth factor gene expression and 2) the effects of ethanol on skeletal muscle growth factor gene expression were independent of exercise-induced growth factor gene expression. Female Wistar rats were used. Four groups (saline + rest; saline + exercise; 17 mmol/kg ethanol + rest; and 17 mmol/kg ethanol + exercise) were used to measure the growth factor response to acute exercise and ethanol administration. Vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), Flt-1, and Flk-1 mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Ethanol increased VEGF, TGF-β1, bFGF, and Flt-1 mRNA at rest and after acute exercise. Ethanol increased resting Flk-1 mRNA. Ethanol increased bFGF mRNA independently of exercise. These findings suggest that 1) ethanol can increase skeletal muscle angiogenic growth factor gene expression and 2) the mechanisms responsible for the ethanol-induced increases in VEGF, TGFβ1, and Flt-1 mRNA appear to be different from those responsible for exercise-induced regulation. Therefore, these results provide evidence in adult rat tissue that the protective cardiovascular effects of moderate ethanol consumption may result in part through the increase of angiogenic growth factors.

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