circUSP13 facilitates the fast-to-slow myofiber shift via the MAPK/ERK signaling pathway in goat skeletal muscles

J Cell Physiol. 2024 May;239(5):e31226. doi: 10.1002/jcp.31226. Epub 2024 Apr 9.

Abstract

Understanding how skeletal muscle fiber proportions are regulated is essential for understanding muscle function and improving the quality of mutton. While circular RNA (circRNA) has a critical function in myofiber type transformation, the specific mechanisms are not yet fully understood. Prior evidence indicates that circular ubiquitin-specific peptidase 13 (circUSP13) can promote myoblast differentiation by acting as a ceRNA, but its potential role in myofiber switching is still unknown. Herein, we found that circUSP13 enhanced slow myosin heavy chain (MyHC-slow) and suppressed MyHC-fast expression in goat primary myoblasts (GPMs). Meanwhile, circUSP13 evidently enhanced the remodeling of the mitochondrial network while inhibiting the autophagy of GPMs. We obtained fast-dominated myofibers, via treatment with rotenone, and further demonstrated the positive role of circUSP13 in the fast-to-slow transition. Mechanistically, activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway significantly impaired the slow-to-fast shift in fully differentiated myotubes, which was restored by circUSP13 or IGF1 overexpression. In conclusion, circUSP13 promoted the fast-to-slow myofiber type transition through MAPK/ERK signaling in goat skeletal muscle. These findings provide novel insights into the role of circUSP13 in myofiber type transition and contribute to a better understanding of the genetic mechanisms underlying meat quality.

Keywords: MAPK/ERK pathway; autophagy; circUSP13; goat myoblasts; mitochondrial; myofiber type transition.

MeSH terms

  • Animals
  • Autophagy / physiology
  • Cell Differentiation
  • Cells, Cultured
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Goats*
  • MAP Kinase Signaling System* / physiology
  • Muscle Development / genetics
  • Muscle Fibers, Fast-Twitch* / metabolism
  • Muscle Fibers, Slow-Twitch* / metabolism
  • Myoblasts / metabolism
  • Myosin Heavy Chains* / genetics
  • Myosin Heavy Chains* / metabolism
  • RNA, Circular* / metabolism

Substances

  • Extracellular Signal-Regulated MAP Kinases
  • Myosin Heavy Chains
  • RNA, Circular