Double-negative feedback loop between IGF2BP2 and miR-196-5p inhibits the proliferation and differentiation of primary chicken myoblasts

Skeletal muscle, the primary edible component of chicken, plays a crucial role in determining meat yield and quality. It was reported that IGF2BP2 plays a critical role in the growth and development of mammals muscle, but its role in poultry muscle development remains poorly understood. Here, we investigated the genetic polymorphism of IGF2BP2 in chickens and identified 43 single nucleotide polymorphisms (SNPs), including 10 SNPs in the coding region, 3 SNPs in the 3' untranslated region (3'UTR), and 30 SNPs in non-coding regions. Notably, 25 loci were significantly associated with growth traits, among which 5 loci showed a strong correlation with body weight. Haplotype analysis also revealed several SNP combinations associated with superior weight, keel length, tibia length and chest width, tibia circumference, and chest depth, suggesting their potential utility in molecular-assisted selection for Yuexi frizzled feather chicken. Furthermore, functional investigation demonstrated that IGF2BP2 suppressed the proliferation and differentiation of chicken myoblasts. Mechanistically, IGF2BP2 was post-transcriptionally inhibited by miR-196-5p, while IGF2BP2 protein reciprocally repressed miR-196-5p precursor expression, forming a regulatory double-negative feedback loop to regulate the myoblast development. These findings highlight IGF2BP2 as a critical regulator of skeletal muscle development in chickens, providing novel insights into its role in growth performance and potential applications in poultry breeding.