Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Biochem Biophys Res Commun. 2019 Jun 30;514(3):848-852. doi: 10.1016/j.bbrc.2019.04.180. Epub 2019 May 10.
Adipogenesis is a differentiation process from mesenchymal stem cells to adipocytes. It has been reported that adipogenesis is regulated by a highly orchestrated transcriptional cascade. However, the effects of modulation of mRNA splicing on adipogenesis remain unknown. To investigate these effects, 3T3-L1 preadipocyte were treated with the potent splicing inhibitor spliceostatin A, which revealed that splicing inhibition suppressed adipogenesis. In addition, treatment of 3T3-L1 cells with spliceostatin A during the early phase of adipogenesis was sufficient to inhibit adipogenesis. In the early phase of adipogenesis, the cells re-entered the cell cycle, which is referred to as mitotic clonal expansion. As mitotic clonal expansion is required for adipogenesis, it was assumed that splicing inhibition would suppress mitotic clonal expansion, and consequently inhibit adipogenesis. As expected, spliceostatin A treatment caused G1 phase arrest and inhibited cell proliferation, i.e., inhibition of mitotic clonal expansion. These results suggest that splicing activity is required for mitotic clonal expansion and adipogenesis.
脂肪生成是从间充质干细胞分化为脂肪细胞的过程。据报道，脂肪生成受高度协调的转录级联调控。然而，mRNA 剪接的调节对脂肪生成的影响尚不清楚。为了研究这些影响，用强效剪接抑制剂 spliceostatin A 处理 3T3-L1 前体脂肪细胞，结果表明剪接抑制抑制了脂肪生成。此外，在脂肪生成的早期阶段用 spliceostatin A 处理 3T3-L1 细胞足以抑制脂肪生成。在脂肪生成的早期阶段，细胞重新进入细胞周期，这被称为有丝分裂克隆扩张。由于有丝分裂克隆扩张是脂肪生成所必需的，因此假设剪接抑制会抑制有丝分裂克隆扩张，从而抑制脂肪生成。正如预期的那样，spliceostatin A 处理导致 G1 期停滞并抑制细胞增殖，即抑制有丝分裂克隆扩张。这些结果表明剪接活性是有丝分裂克隆扩张和脂肪生成所必需的。
