Long noncoding RNA Neat1 modulates myogenesis by recruiting Ezh2

Neat1 is widely expressed in many tissues and cells and exerts pro-proliferation effects on many cancer cells. However, little is known about the function of Neat1 in myogenesis. Here we characterized the roles of Neat1 in muscle cell formation and muscle regeneration. Gain- or loss-of-function studies in C2C12 cells demonstrated that Neat1 accelerates myoblast proliferation but suppresses myoblast differentiation and fusion. Further, knockdown of Neat1 in vivo increased the cross-sectional area of muscle fibers but impaired muscle regeneration. Mechanically, Neat1 physically interacted with Ezh2 mainly through the core binding region (1001–1540 bp) and recruited Ezh2 to target gene promoters. Neat1 promoted myoblast proliferation mainly by decreasing the expression of the cyclin-dependent kinase inhibitor P21 gene but inhibited myoblast differentiation by suppressing the transcription of myogenic marker genes, such as Myog, Myh4, and Tnni2. Altogether, we uncover a previously unknown function of Neat1 in muscle development and the molecular mechanism by which Neat1 regulates myogenesis.