WNT5B regulates myogenesis and fiber type conversion by affecting mRNA stability.

The wingless-integrated (WNT) signaling pathway is known to play a critical role in myogenesis. WNT5B, a member of the WNT family, is essential for determining cell fate and development. However, the molecular mechanisms by which WNT5B regulates myogenesis remain unclear. This study observed that WNT5B, which is conserved between mice and pigs, is highly expressed in the skeletal muscle. The expression of WNT5B was varied in the skeletal muscle between the Tongcheng (obese-type) and Landrace (lean-type) pigs. In vitro, WNT5B promoted skeletal muscle cell proliferation and cell cycle progression, while inhibited cell apoptosis. In vivo, WNT5B promoted myofiber thickness and increased slow-type muscle fibers in porcine skeletal muscles. Mechanically, a SNP site (c.1608 A > G) located in the 3' untranslated region (3'UTR) of WNT5B regulated transcript attenuation and acts through AU-rich element mediation (ARE) to influence myogenesis. Also, the SNP was located in the miRNA response element of miR-29a/b/c to influence WNT5B expression. However, ARE sites did not affect the binding relationship of miR-29a/b/c. In conclusion, this study demonstrated that the SNP (c.1608 A > G) affects WNT5B mRNA stability by protecting the 3'UTR of the WNT5B from the degrading effects of miR-29a/b/c. This study reveals the critical role of WNT5B in myogenesis and indicates that it is a novel candidate gene for pig breeding.