CircMAPK1-encoded micropeptide circMAPK1-110aa inhibits proliferation and differentiation of goat skeletal muscle satellite cells by suppressing MAPK1/3 phosphorylation

  • Int J Biol Macromol. 2026 May:364:152258. doi: 10.1016/j.ijbiomac.2026.152258.
Qianqian Pan  1 ,  Mengyu Lou  1 ,  Mengkang Zhu  1 ,  Xiaohong He  2 ,  Xianyong Lan  3 ,  Sihuan Zhang  1 ,  Yinghui Ling  4
Affiliations
  • 1. College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, 230036, China; Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Germplasm Innovation, Anhui Agricultural University, Hefei, 230036, Anhui, China.
  • 2. National Germplasm Center of Domestic Animal Resources, Ministry of Technology, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China.
  • 3. College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
  • 4. College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui, 230036, China; Anhui Province Key Laboratory of Local Livestock and Poultry Genetic Resource Conservation and Germplasm Innovation, Anhui Agricultural University, Hefei, 230036, Anhui, China. Electronic address: [email protected].
PMID: 42055358 DOI: 10.1016/j.ijbiomac.2026.152258
Abstract

Skeletal muscle development directly determines growth efficiency and meat quality in livestock. Circular RNAs (circRNAs) and their encoded micropeptides are emerging regulators of this process, yet their roles in goats remain poorly understood. Through integrated ribosome profiling (Ribo-seq) and circRNA-seq of goat skeletal muscle satellite cells (SMSCs), we identified a MAPK1-derived protein-coding circRNA, circMAPK1 (novel-circ-0039015). Functional analyses revealed that circMAPK1 overexpression suppressed SMSCs proliferation and myogenic differentiation. Mechanistically, circMAPK1 encodes a 110-amino-acid micropeptide (circMAPK1-110aa) that binds Mitogen-Activated Protein Kinase Kinase 1 (MAP2K1) and reduces MAPK1/3 phosphorylation, thereby attenuating Mitogen-Activated Protein Kinase (MAPK) signaling. Importantly, pharmacological activation of the MAPK pathway with C16-PAF partially restored muscle cell growth and differentiation. These findings establish circMAPK1 as a negative regulator of goat skeletal muscle development and highlight its encoded micropeptides as a potential molecular target. By uncovering a new regulatory mechanism of muscle growth, this study provides valuable insights for breeding strategies aimed at enhancing meat yield and quality in goats.

Keywords
CircMAPK1; Goat; MAPK signaling pathway; Micropeptide; Skeletal muscle development.
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