| First Author | Huot MÉ | Year | 2012 |
| Journal | Mol Cell | Volume | 46 |
| Issue | 2 | Pages | 187-99 |
| PubMed ID | 22424772 | Mgi Jnum | J:188028 |
| Mgi Id | MGI:5438911 | Doi | 10.1016/j.molcel.2012.02.007 |
| Citation | Huot ME, et al. (2012) The Sam68 STAR RNA-binding protein regulates mTOR alternative splicing during adipogenesis. Mol Cell 46(2):187-99 |
| abstractText | We report that mice ablated for the Sam68 RNA-binding protein exhibit a lean phenotype as a result of increased energy expenditure, decreased commitment to early adipocyte progenitors, and defects in adipogenic differentiation. The Sam68(-/-) mice were protected from obesity, insulin resistance, and glucose intolerance induced with a high-fat diet. To identify the alternative splice events regulated by Sam68, genome-wide exon usage profiling in white adipose tissue was performed. Adipocytes from Sam68(-/-) mice retained intron 5 within the mTOR transcript introducing a premature termination codon, leading to an unstable mRNA. Consequently, Sam68-depleted cells had reduced mTOR levels resulting in lower levels of insulin-stimulated S6 and Akt phosphorylation leading to defects in adipogenesis, and this defect was rescued by the exogenous expression of full-length mTOR. Sam68 bound intronic splice elements within mTOR intron 5 required for the usage of the 5' splice site. We propose that Sam68 regulates alternative splicing during adipogenesis. |
