Yang Xinran, Mei Chugang, Ma Xinhao, Du Jiawei, Wang Jianfang, Zan Linsen
College of Animal Science and Technology, Northwest A & F University, Xianyang 712100, China.
National Beef Cattle Improvement Center, Northwest A & F University, Xianyang 712100, China.
Animals (Basel). 2022 Mar 18;12(6):773. doi: 10.3390/ani12060773.
-methyladenosine (mA) plays an important role in regulating gene expression. Previous studies found that mA methylation affects skeletal muscle development. However, the effect of mA methylases on bovine skeletal myogenesis is still unclear. Here, we found that the expression of mA demethylases ( and ) was significantly higher in the longissimus dorsi muscle of adult cattle than in newborn cattle. In contrast, the expression of mA methyltransferases (, and ) was reduced. The mRNA expression of all five genes was found to be increased during the myogenesis of myoblasts in vitro. Knockdown of FTO or METTL3 promoted myoblast proliferation, inhibited myoblast apoptosis and suppressed myogenic differentiation, whereas ALKBH5 knockdown had the opposite effect. METTL14 knockdown enhanced myoblast proliferation and impaired myogenic differentiation. WTAP knockdown attenuated proliferation and contributed to apoptosis but did not affect differentiation. Furthermore, the functional domains of these five mA methylases are conserved across species. Our results suggest that mA methylases are involved in regulating skeletal muscle development and that there may be a complex network of mA methylation regulating skeletal myogenesis.
N6-甲基腺苷（mA）在调节基因表达中起重要作用。先前的研究发现，mA甲基化影响骨骼肌发育。然而，mA甲基化酶对牛骨骼肌生成的影响仍不清楚。在此，我们发现，成年牛背最长肌中mA去甲基化酶（FTO和ALKBH5）的表达显著高于新生牛。相反，mA甲基转移酶（METTL3、METTL14和WTAP）的表达降低。在体外成肌细胞生成过程中，发现所有这五个基因的mRNA表达均增加。敲低FTO或METTL3可促进成肌细胞增殖、抑制成肌细胞凋亡并抑制肌源性分化，而敲低ALKBH5则产生相反的效果。敲低METTL14可增强成肌细胞增殖并损害肌源性分化。敲低WTAP可减弱增殖并导致凋亡，但不影响分化。此外，这五种mA甲基化酶的功能域在物种间是保守的。我们的结果表明，mA甲基化酶参与调节骨骼肌发育，并且可能存在一个复杂的mA甲基化网络调节骨骼肌生成。
