GPCPD1 is regulated by METTL3/IGF2BP3 dependent m6A modification to affect pig muscle fiber type conversion

Yuming Yang; Baohua Tan; Liyao Xiao; Huijun Huang; Weihua Xu; Jiawei Su; Yaolu Zhao; Linjun Hong; Gengyuan Cai; Zicong Li; Lihe Dai; Ting Gu

doi:10.1016/j.gene.2025.149578

GPCPD1 is regulated by METTL3/IGF2BP3 dependent m⁶A modification to affect pig muscle fiber type conversion

Gene. 2025 Aug 20:962:149578. doi: 10.1016/j.gene.2025.149578. Epub 2025 May 20.

Authors

Yuming Yang¹, Baohua Tan², Liyao Xiao¹, Huijun Huang¹, Weihua Xu³, Jiawei Su¹, Yaolu Zhao⁴, Linjun Hong¹, Gengyuan Cai¹, Zicong Li¹, Lihe Dai⁵, Ting Gu⁶

Affiliations

¹ National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, Guangzhou, China.
² The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ College of Life Science, Longyan University, Longyan, China.
⁴ Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.
⁵ Key Laboratory of Animal Genetics and Breeding of Zhejiang Province, Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou, China. Electronic address: dailh@zaas.ac.cn.
⁶ National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, Guangzhou, China. Electronic address: tinggu@scau.edu.cn.

PMID: 40404071
DOI: 10.1016/j.gene.2025.149578

Abstract

The N6-methyladenosine (m⁶A) modification is the most prevalent and abundant RNA modification in eukaryotes. In our previous study, we identified that the glycerophosphocholine phosphodiesterase 1 (GPCPD1) gene was differentially expressed and diverse m⁶A modificated in the pig soleus and extensor digitorum longus muscles. In this study, we further investigated the function of GPCPD1 gene in pig muscle development. We found that GPCPD1 inhibited myogenic differentiation and promoted the conversion of fast-twitch to slow-twitch fibers in both porcine muscle satellite cells (PSCs) and in mouse model. We also found that the expression of GPCPD1 was affected by m⁶A methyltransferase METTL3. The methylated GPCPD1 gene was recognized by the m⁶A reader protein IGF2BP3, which further modulated the stability of GPCPD1 mRNA. This study provided novel evidence into m⁶A regulation in pig muscle development and illustrated the new post-transcriptional regulation way in GPCPD1 expression.

Keywords: GPCPD1; Muscle fiber type conversion; Myogenic differentiation; Pig; m(6)A.

MeSH terms

Adenosine* / analogs & derivatives
Adenosine* / metabolism
Animals
Cell Differentiation / genetics
Methyltransferases* / genetics
Methyltransferases* / metabolism
Mice
Muscle Development / genetics
Muscle Fibers, Fast-Twitch / metabolism
Muscle Fibers, Slow-Twitch / metabolism
RNA-Binding Proteins* / genetics
RNA-Binding Proteins* / metabolism
Satellite Cells, Skeletal Muscle / cytology
Satellite Cells, Skeletal Muscle / metabolism
Swine

Substances

Methyltransferases
N-methyladenosine
Adenosine
RNA-Binding Proteins