| First Author | Fujita R | Year | 2021 |
| Journal | Development | Volume | 148 |
| Issue | 2 | PubMed ID | 33318147 |
| Mgi Jnum | J:301550 | Mgi Id | MGI:6505244 |
| Doi | 10.1242/dev.194480 | Citation | Fujita R, et al. (2021) Satellite cell expansion is mediated by P-eIF2alpha-dependent Tacc3 translation. Development 148(2):dev194480 |
| abstractText | Translational 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 eIF2alpha (P-eIF2alpha). Pharmacological inhibition of the eIF2alpha phosphatase with the small molecule sal003 maintains P-eIF2alpha and permits the expansion of satellite cells ex vivo Paradoxically, P-eIF2alpha also increases the translation of specific mRNAs, which is mediated by P-eIF2alpha-dependent read-through of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2alpha-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-eIF2alpha-dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle. |
