Institute of Sheep and Goat Science, Nanjing Agricultural University, Nanjing, 210095, China.
Department of Pathology, School of Medicine, Jiangsu University, Zhenjiang, 212000, China.
Exp Cell Res. 2021 Apr 15;401(2):112524. doi: 10.1016/j.yexcr.2021.112524. Epub 2021 Feb 27.
N6-Methyladenosine (mA) modification is the most abundant chemical modification in mRNA, and it participates in various biological processes, such as cell differentiation and proliferation. However, little is known about the function of mA demethylase fat mass and obesity-associated (FTO) in myoblast proliferation. Here, we demonstrated that knockdown of FTO can significantly inhibit myoblast proliferation and promote apoptosis. RNA sequencing analysis revealed that a lot of downregulated genes in FTO knockdown cells are associated with cell cycle and apoptosis. Furthermore, silencing FTO drastically decreased cyclin D1 (CCND1) expression through YTHDF2-mediated mRNA degradation, thereby delaying the progression of G1 phase, and leading to impaired myoblast proliferation. These findings unraveled that FTO regulates myoblast proliferation by controlling CCND1 expression in an mA-YTHDF2-dependent manner, which highlights the critical roles of mA modification in myoblast proliferation.
N6-甲基腺苷（mA）修饰是 mRNA 中最丰富的化学修饰，它参与多种生物学过程，如细胞分化和增殖。然而，mA 去甲基酶肥胖相关蛋白（FTO）在成肌细胞增殖中的功能知之甚少。在这里，我们证明了 FTO 的敲低可以显著抑制成肌细胞的增殖并促进细胞凋亡。RNA 测序分析表明，FTO 敲低细胞中大量下调的基因与细胞周期和细胞凋亡有关。此外，沉默 FTO 通过 YTHDF2 介导的 mRNA 降解显著降低细胞周期蛋白 D1（CCND1）的表达，从而延缓 G1 期的进展，导致成肌细胞增殖受损。这些发现揭示了 FTO 通过 mA-YTHDF2 依赖性方式控制 CCND1 表达来调节成肌细胞增殖，这凸显了 mA 修饰在成肌细胞增殖中的关键作用。
