FTO regulates myoblast proliferation by controlling CCND1 expression in an m6A-YTHDF2-dependent manner

Abstract

N6-Methyladenosine (m⁶A) 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 m⁶A 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 m⁶A-YTHDF2-dependent manner, which highlights the critical roles of m⁶A modification in myoblast proliferation.

Keywords: Cell cycle; Cell proliferation; FTO; Myoblast; m(6)A modification.