| First Author | Crawford Parks TE | Year | 2017 |
| Journal | Hum Mol Genet | Volume | 26 |
| Issue | 10 | Pages | 1821-1838 |
| PubMed ID | 28369467 | Mgi Jnum | J:242354 |
| Mgi Id | MGI:5905079 | Doi | 10.1093/hmg/ddx085 |
| Citation | Crawford Parks TE, et al. (2017) Muscle-specific expression of the RNA-binding protein Staufen1 induces progressive skeletal muscle atrophy via regulation of phosphatase tensin homolog. Hum Mol Genet 26(10):1821-1838 |
| abstractText | Converging lines of evidence have now highlighted the key role for post-transcriptional regulation in the neuromuscular system. In particular, several RNA-binding proteins are known to be misregulated in neuromuscular disorders including myotonic dystrophy type 1, spinal muscular atrophy and amyotrophic lateral sclerosis. In this study, we focused on the RNA-binding protein Staufen1, which assumes multiple functions in both skeletal muscle and neurons. Given our previous work that showed a marked increase in Staufen1 expression in various physiological and pathological conditions including denervated muscle, in embryonic and undifferentiated skeletal muscle, in rhabdomyosarcomas as well as in myotonic dystrophy type 1 muscle samples from both mouse models and humans, we investigated the impact of sustained Staufen1 expression in postnatal skeletal muscle. To this end, we generated a skeletal muscle-specific transgenic mouse model using the muscle creatine kinase promoter to drive tissue-specific expression of Staufen1. We report that sustained Staufen1 expression in postnatal skeletal muscle causes a myopathy characterized by significant morphological and functional deficits. These deficits are accompanied by a marked increase in the expression of several atrophy-associated genes and by the negative regulation of PI3K/AKT signaling. We also uncovered that Staufen1 mediates PTEN expression through indirect transcriptional and direct post-transcriptional events thereby providing the first evidence for Staufen1-regulated PTEN expression. Collectively, our data demonstrate that Staufen1 is a novel atrophy-associated gene, and highlight its potential as a biomarker and therapeutic target for neuromuscular disorders and conditions. |
